Increased DNA methylation of the splicing regulator SR45 suppresses seed abortion in litchi.

The gene regulatory networks that govern seed development are complex, yet very little is known about the genes and processes that are controlled by DNA methylation. Here, we performed single-base resolution DNA methylome analysis and found that CHH methylation increased significantly throughout seed development in litchi. Based on the association analysis of differentially methylated regions and weighted gene co-expression network analysis (WGCNA), 46 genes were identified as essential DNA methylation-regulated candidate genes involved in litchi seed development, including LcSR45, a homolog of the serine/arginine-rich (SR) splicing regulator SR45. LcSR45 is predominately expressed in the funicle, embryo, and seed integument, and displayed increased CHH methylation in the promoter during seed development. Notably, silencing of LcSR45 in a seed-aborted litchi cultivar significantly improved normal seed development, whereas the ectopic expression of LcSR45 in Arabidopsis caused seed abortion. Furthermore, LcSR45-dependent alternative splicing events were found to regulate genes involved in seed development. Together, our findings demonstrate that LcSR45 is hypermethylated, and plays a detrimental role in litchi seed development, indicating a global increase in DNA methylation at this stage.

Does an antihypertensive diet cost more? Analysis from the Chinese Heart-Healthy diet trial.

OBJECTIVE: To determine whether the Chinese heart-healthy diet (Sichuan cuisine version) (CHH diet-SC) was more expensive than the conventional Sichuan diet and explore the food groups and nutrients that mainly affected the cost of CHH diet-SC. DESIGN: Cost analysis of 4-week intervention diets in the Sichuan center representing southwestern China in the CHH diet study. SETTING: A multicentre, parallel-group, single-blind, randomised feeding trial evaluating the efficacy of lowering blood pressure with the cuisine-based CHH diet. PARTICIPANTS: Totally, fifty-three participants with hypertension aged 25-75 years in the Sichuan center were randomised into the control group (n 26) or the CHH diet-SC group (n 27). RESULTS: The CHH diet-SC was more expensive than the control diet (¥27·87 ± 2·41 v. ¥25·18 ± 2·79 equals $3·90 ± 0·34 v. $3·52 ± 0·39, P < 0·001), and the incremental cost-effectiveness ratio for a 1-mm Hg systolic blood pressure reduction was ¥9·12 ($1·28). Intakes and the cost of seafood, dairy products, fruits, soybeans and nuts, whole grains and mixed beans were higher for the CHH diet-SC than for the control diet (P < 0·001). Intakes of vitamin B1, vitamin B6, vitamin C, Mg and phosphorus were positively correlated with the cost (P < 0·05). CONCLUSIONS: The CHH diet-SC costs more than the conventional Sichuan diet, partly due to the high cost of specific food groups. Positive correlations between the intakes of vitamin B1, vitamin B6, vitamin C, Mg, phosphorus and the dietary cost could be a direction to adjust the composition within the food groups to reduce the cost of the CHH diet-SC.

[Cross-Sectional Study of Nutritional Service Capacity for Infants and Toddlers in Urban and Rural Medical Facilities in Sichuan Province]. / å››å·çœåŸŽä¹¡åŒ»ç–—æœºæž„å©´å¹¼å„¿è¥å »æœåŠ¡èƒ½åŠ›çŽ°å†µç ”ç©¶.

Objective: To investigate and analyze the current status and challenges of infant and toddler nutritional services in urban and rural medical facilities in Sichuan Province. Methods: In 2022, a questionnaire survey was conducted to collect data on infant and toddler nutritional services, including feeding guidance, physical growth assessment, and micronutrient deficiency screening, as well as information on personnel and tools in medical facilities throughout Sichuan Province. The provision of nutritional services was analyzed and the urban-rural disparities were assessed. Results: A total of 2206 medical facilities (29.1% from urban areas and 70.9% from rural areas) were investigated. Only 35.8% of medical facilities provided all three types of nutritional services. Specifically, the overall service provision rates were high for feeding guidance (94.6%) and physical growth assessment (85.0%), but lower for micronutrient deficiency screening (37.4%). Rural facilities exhibited significantly lower rates than their urban counterparts for both physical growth assessment and micronutrient deficiency screening (P<0.05). The provision rates of feeding guidance ranged from 70.6% to 93.2%, with responsive feeding guidance being the least implemented (70.6%), particularly in rural areas compared to urban areas (P<0.05). Rates for physical growth assessment and micronutrient deficiency screening ranged from 75.3% to 81.8% and 23.6% to 30.8%, respectively, both showing lower rates in rural settings compared to urban ones (P<0.05). Nutrition service providers were predominantly nurses (52.3%) and clinical practitioners (43.4%). The availability of dietary assessment tools ranged from 7.7% to 15.9%, significantly lower in rural areas compared to urban areas (P<0.001), while physical measurement tools were widely available at rates of 94.6% to 98.5%. Conclusion: At present, the infant and toddler nutritional service provisions of medical facilities in Sichuan Province are incomplete, particularly so in the implementation of feeding guidance, physical growth assessment, and micronutrient deficiency screening. There is a notable shortage of personnel and necessary tools, with rural areas facing more significant challenges. Enhancing the overall capacity of infant and toddler nutritional services in Sichuan Province is essential, with specific attention needed for rural healthcare settings.

Nifuroxazide ameliorates pulmonary fibrosis by blocking myofibroblast genesis: a drug repurposing study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease with a complex pathogenesis and high mortality. The development of new drugs is time-consuming and laborious; therefore, research on the new use of old drugs can save time and clinical costs and even avoid serious side effects. Nifuroxazide (NIF) was originally used to treat diarrhoea, but more recently, it has been found to have additional pharmacological effects, such as anti-tumour effects and inhibition of inflammatory diseases related to diabetic nephropathy. However, there are no reports regarding its role in pulmonary fibrosis. METHODS: The therapeutic effect of NIF on pulmonary fibrosis in vivo was measured by ELISA, hydroxyproline content, H&E and Masson staining, immunohistochemistry (IHC) and western blot. Immune cell content in lung tissue was also analysed by flow cytometry. NIF cytotoxicity was evaluated in NIH/3T3 cells, human pulmonary fibroblasts (HPFs), A549 cells and rat primary lung fibroblasts (RPLFs) using the MTT assay. Finally, an in vitro cell model created by transforming growth factor-ß1 (TGF-ß1) stimulation was assessed using different experiments (immunofluorescence, western blot and wound migration assay) to evaluate the effects of NIF on the activation of NIH/3T3 and HPF cells and the epithelial-mesenchymal transition (EMT) and migration of A549 cells. RESULTS: In vivo, intraperitoneal injection of NIF relieved and reversed pulmonary fibrosis caused by bleomycin (BLM) bronchial instillation. In addition, NIF inhibited the expression of a variety of cellular inflammatory factors and immune cells. Furthermore, NIF suppressed the activation of fibroblasts and EMT of epithelial cells induced by TGF-ß1. Most importantly, we used an analytical docking experiment and thermal shift assay to further verify that NIF functions in conjunction with signal transducer and activator of transcription 3 (Stat3). Moreover, NIF inhibited the TGF-ß/Smad pathway in vitro and decreased the expression of phosphorylated Stat3 in vitro and in vivo. CONCLUSION: Taken together, we conclude that NIF inhibits and reverses pulmonary fibrosis, and these results support NIF as a viable therapeutic option for IPF treatment.

Performance of 18 F-FAPI PET/CT in assessing glioblastoma before radiotherapy: a pilot study.

BACKGROUND: We aimed to determine the performance of 18 F-FAPI PET/CT used for preprocedural assessment of glioblastoma before radiotherapy. METHODS: Twelve glioblastoma patients having undergone incomplete surgical resection or biopsy were examined with 18 F-FAPI PET/CT and MRI scanning before radiotherapy. All patients had confirmed tumor residues according to findings of histopathological and/or long-term clinical and radiological follow-ups. Lesion characterization data, including SUVmax and tumor-to-background ratio (TBR) on PET/CT were attained. PET/CT and MRI findings were compared in terms of number of lesions. The correlation between immunohistochemistry, molecular expression, and PET/CT parameters was also evaluated. RESULTS: 18 F-FAPI PET/CT detected 16 FAPI-avid out of 23 lesions in 12 patients described on MRI. MRI was statistically different from 18 F-FAPI PET/CT for lesion detection according to the exact McNemar statistical test (P = 0.0156). The SUVmax and TBR of the glioblastomas was 7.08 ± 3.55 and 19.95 ± 13.22, respectively. The sensitivity and positive predictive value (PPV) of 18 F-FAPI PET were 69.6% and 100%, respectively. Neither the Ki-67 index nor the molecular expression was correlated with the FAPI-PET/CT parameters. CONCLUSION: 18 F-FAPI PET/CT detects glioblastomas at a lower rate than MRI. However, the 100% PPV of the examination may make it useful for differentiating controversial lesions detected on MRI. The 18 F-FAPI-avid lesions are displayed more clearly probably due to a higher TBR. 18 F-FAPI PET/CT imaging might find application in glioblastoma biopsy and radiotherapy planning.

A Contrastive Learning Pre-Training Method for Motif Occupancy Identification.

Motif occupancy identification is a binary classification task predicting the binding of DNA motif instances to transcription factors, for which several sequence-based methods have been proposed. However, through direct training, these end-to-end methods are lack of biological interpretability within their sequence representations. In this work, we propose a contrastive learning method to pre-train interpretable and robust DNA encoding for motif occupancy identification. We construct two alternative models to pre-train DNA sequential encoder, respectively: a self-supervised model and a supervised model. We augment the original sequences for contrastive learning with edit operations defined in edit distance. Specifically, we propose a sequence similarity criterion based on the Needleman-Wunsch algorithm to discriminate positive and negative sample pairs in self-supervised learning. Finally, a DNN classifier is fine-tuned along with the pre-trained encoder to predict the results of motif occupancy identification. Both proposed contrastive learning models outperform the baseline end-to-end CNN model and SimCLR method, reaching AUC of 0.811 and 0.823, respectively. Compared with the baseline method, our models show better robustness for small samples. Specifically, the self-supervised model is proved to be practicable in transfer learning.

Galangin ameliorated pulmonary fibrosis in vivo and in vitro by regulating epithelial-mesenchymal transition.

Pulmonary fibrosis (PF) is a disease that is characterized by abnormal epithelial-mesenchymal transition (EMT) and persistent inflammatory injury, with high mortality and poor prognosis, but the current therapies are accompanied by certain adverse side effects. In this study, we investigated the role of galangin (GA), an anti-inflammatory and anti-tumoral phytochemical extracted from galangal, in preventing and curing bleomycin (BLM)-induced pulmonary fibrosis and the underlying mechanism. Histopathological staining confirmed that GA dramatically moderated bleomycin-induced pulmonary fibrosis in mice. Compared with the vehicle treatment, GA treatment inhibited the expression of vimentin and increased the expression of E-cadherin. The expression of α-Smooth muscle actin (α-SMA), which is a myofibroblast marker, was also suppressed. In addition, GA diminished the increase in the numbers of CD4+CD69+ and CD8+CD69+ T cells and dendritic cells induced by bleomycin, and reduced the residence of inflammatory cells in the lung tissues. Notably, GA inhibited the TGF-ß1-induced EMT and fibroblast differentiation in vitro, which further confirmed the potential protective effect of GA on pulmonary fibrosis. Taken together, our results suggest that GA exerts a beneficial effect on bleomycin-induced pulmonary fibrosis by attenuating EMT and inflammatory damage and may have prevent potential of pulmonary fibrosis.

Cryptotanshinone reverses the epithelial-mesenchymal transformation process and attenuates bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial pneumonia that causes pulmonary tissue damage and functional impairment. To investigate the effects of cryptotanshinone on pulmonary fibrosis, the expression of NIH/3T3, HPF, and rat primary pulmonary fibroblasts was measured and found to be inhibited by CPT in a time- and concentration-dependent manner, and the upregulation of α-SMA expression in NIH/3T3 and HPF cells, which had been stimulated by TGFß-1, was decreased after CPT administration. We observed that CPT could reverse the increase in α-SMA expression and vimentin and the decrease in E-cad expression in A549 cells, which had been induced by 5 ng/mL TGFß-1, indicating that CPT has inhibitory effects in the EMT process. A BLM-induced pulmonary fibrosis model was established in C57BL/6 mice. The lung coefficient and hydroxyproline content increased significantly in the BLM-induced group and were decreased in the CPT-treated group. The expression levels of collagen-I and α-SMA and the phosphorylation level of Stat3 were significantly increased, and CPT treatment decreased these levels. Furthermore, the results from the flow cytometry analysis indicated that, in lung tissues, the frequencies of MDSCs, macrophages, DCs and T cells were considerably increased in the BLM-induced group, while CPT treatment reduced these immunocyte populations.

[Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with ß-Glucan].

OBJECTIVE: To provide a scientific evaluation of the food safety of the rice biofortified with ß-glucan. METHODS: The acute toxicity and genotoxicity of the rice were evaluated by 14-day feeding experiment, Ames experiment, erythrocyte micronucleus test and mouse lymphoma thymidine kinase gene ( TK) mutation assay respectively. RESULTS: In the acute toxicity test, there was no obvious toxicity of rice biofortified with ß-glucan, and no abnormality was found in anatomical observation. The median lethal dose (LD 50) to rats and mice wereall greater than 15 mg/kg, which belonged to the actual non-toxic level. Whether with S 9 activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. No induction of polychromatic erythrocytes and inhibition of bone marrow were found in erythrocyte micronucleus test. The results of TK gene mutation assay did not show the mutagenicity of ß-glucan bioaugmentation rice. All results of the three genotoxicity tests were negative. CONCLUSION: Under the current experimental conditions, ß-glucan biofortified rice showed no obvious acute toxicity and genotoxicity.

Natural product pectolinarigenin exhibits potent anti-metastatic activity in colorectal carcinoma cells in vitro and in vivo.

Colorectal carcinoma (CRC) is one of the most common cancers with high metastatic potential, explaining why identifying new drug candidates that inhibit tumour metastasis is an urgent need. The aim of this study was to evaluate the biological activities of pectolinarigenin (PEC, a natural flavonoid present in Cirsium chanroenicum) in CRC in vitro and in vivo and to determine its underlying mechanism of action. Here, we observed that treatment with PEC could inhibit cell viability and induce apoptosis in cancer cells in a concentration- and time-dependent manner. The occurrence of apoptosis was associated with activation of caspase-3 and Bax and decreased expression of Bcl-2. In addition, PEC markedly impaired CRC cell migration and invasion by downregulating the expression of matrix metalloproteinase (MMP-9) and phosphorylated-Stat3Tyr705. Moreover, our studies showed that PEC inhibited abdominal metastasis models of murine colorectal cancer. In addition, histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, MMP9-positive cells and p-Stat3Tyr705 cells upon treatment with PEC compared to control samples. Furthermore, PEC reduced the number of myeloid-derived suppressor cells (MDSCs) in the blood and tumours, which was accompanied by the increased infiltration of CD8+T cells in the blood. Taken together, our findings suggested that PEC could be used as a natural drug to inhibit CRC metastasis.

[The Extract from Punica Granatum (Pomegranate) Leaves Promotes Apoptosis and Impairs Metastasis in Prostate Cancer Cells].

OBJECTIVE: To investigate the effects of pomegranate leaves extract(PLE)on proliferation,apoptosis and metastasis of prostate cancer cells. METHODS: The proliferation of TRAMP-C1,DU145,PC3 prostate cancer cells treated with different concentrations of PLE (final mass concentrations were 12.5,25,50,100, 200 µg/mL,respectively) for different time (24,48,72 h) was detected by MTT assay. Colony formation assay was performed to verify the long-term effects of PLE on the proliferation of DU145 and PC3 cells.After being treated with PLE for 48 h,Hoechst-33258 staining was used to observe the changes in the nucleus,the cell apoptotic rate was detected by flow cytometry,and wound-healing migration assay was perform to test the change of migration. RESULTS: In comparison with the control group,PLE in the range of 12.5-200 µg/mL had a certain inhibitory effect on the proliferation of TRAMP-C1,DU145 and PC3 cells ( P<0.05).In the range of 6.25-100 µg/mL,the number of colony formation of DU145 and PC3 was significantly reduced( P<0.01).After PLE treated for 48 h, the apoptotic features of nuclear fragmentation and the formation apoptotic body was observed in PC3. With the increase of concentration,the apoptotic rate increased gradually ( P<0.05),and the ability of cells to migrate to the scratch area was significantly weaker than the control group ( P<0.01). CONCLUSION: PLE has effect on proliferation,apoptosis and metastasis of prostate cancer cells.

SCINet: A Segmentation and Classification Interaction CNN Method for Arteriosclerotic Retinopathy Grading.

As a common disease, cardiovascular and cerebrovascular diseases pose a great harm threat to human wellness. Even using advanced and comprehensive treatment methods, there is still a high mortality rate. Arteriosclerosis, as an important factor reflecting the severity of cardiovascular and cerebrovascular diseases, is imperative to detect the arteriosclerotic retinopathy. However, the detection of arteriosclerosis retinopathy requires expensive and time-consuming manual evaluation, while end-to-end deep learning detection methods also need interpretable design to high light task-related features. Considering the importance of automatic arteriosclerotic retinopathy grading, we propose a segmentation and classification interaction network (SCINet). We propose a segmentation and classification interaction architecture for grading arteriosclerotic retinopathy. After IterNet is used to segment retinal vessel from original fundus images, the backbone feature extractor roughly extracts features from the segmented and original fundus arteriosclerosis images and further enhances them through the vessel aware module. The last classifier module generates fundus arteriosclerosis grading results. Specifically, the vessel aware module is designed to highlight the important areal vessel features segmented from original images by attention mechanism, thereby achieving information interaction. The attention mechanism selectively learns the vessel features of segmentation region information under the proposed interactive architecture, which leads to reweighting the extracted features and enhances significant feature information. Extensive experiments have confirmed the effect of our model. SCINet has the best performance on the task of arteriosclerotic retinopathy grading. Additionally, the CNN method is scalable to similar tasks by incorporating segmented images as auxiliary information.

Rosa sterilis Juice Alleviated Breast Cancer by Triggering the Mitochondrial Apoptosis Pathway and Suppressing the Jak2/Stat3 Pathway.

Rosa sterilis (RS) is a characteristic fruit in southwestern China that has numerous health benefits; however, its pharmacological effect needs further clarification, especially with respect to the exploration of its potential anti-breast-cancer effect, as there are still knowledge gaps in this regard. This study was designed to investigate the protective effects of Rosa sterilis juice (RSJ) on breast cancer (BC) through in vitro cellular experiments and by establishing mouse 4T1 breast xenograft tumors. This study also had the aim of elucidating RSJ's underlying mechanisms. RSJ can inhibit cell proliferation, affect cell morphology, and impact the clone formation ability of BC; furthermore, it can promote apoptosis by triggering the mitochondrial apoptosis pathway. In mouse 4T1 breast xenograft tumors, RSJ markedly inhibited tumor growth, relieved the pathological lesions, lowered the expression of Ki67, and regulated the expression of the apoptosis-associated protein. Moreover, we observed that RSJ can inhibit the Jak2/Stat3 signaling pathway both in vivo and in vitro. Overall, our research reveals that RSJ can alleviate BC by triggering the mitochondrial apoptosis pathway and suppressing the Jak2/Stat3 pathway, providing new dietary intervention strategies for BC.

Pomegranate juice-containing serum inhibits migration of hepatocellular carcinoma cells and promotes apoptosis by induction of mitochondrial dysfunction.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with an insidious onset and poor prognosis. Pomegranate is a fruit rich in many natural products with anti-cancer potential; however, its direct biological effects are difficult to evaluate in vitro because of changes in its active components after absorption and metabolism. This study was conducted to prepare pomegranate juice-containing serum (PJ serum) by gavage of pomegranate juice (PJ) in rats and to collect serum. The aim was to investigate the components and the effects of PJ serum on HCC cells by serum pharmacology. 56 compounds were identified in the PJ serum, including 6 prototype components. PJ serum selectively inhibited HCC cells proliferation and migration, and it promoted apoptosis of HCC cells without affecting LO2 cells activity. Furthermore, PJ serum reduced the mitochondrial membrane potential and increased the calcium ion concentration in HCC cells. Mechanistically, PJ serum up-regulated the expression of the Bax family, Caspases and TIMP2/MMP2, and down-regulated the expression of MMP9. This study revealed that PJ serum inhibited HCC cell migration by regulating the TIMP2/MMP2 balance and MMP9 expression and promoted HCC cell apoptosis by inducing mitochondrial dysfunction and causing a Caspase cascade. The polyphenols and flavonoids in PJ may be important components responsible for its anti-HCC activity after metabolism.

Anlotinib as Monotherapy or Combination Therapy for Recurrent High-Grade Glioma: A Retrospective Study.

Background: Anlotinib is a multi-target anti-angiogenic agent. The retrospective study was conducted to evaluate the safety and effectiveness of anlotinib as monotherapy or combination therapy for the treatment of recurrent high-grade gliomas. Methods: In this retrospective study, patients with recurrent high-grade glioma (according to the 2021 World Health Organization classification as levels III-IV) at Sichuan Cancer Hospital from June 2019 to June 2022 were included. The patients were divided into an anlotinib-monotherapy group and an anlotinib-combination group, and received oral anlotinib 8 to 12 mg once a day, with 2 weeks on/1 week off. The primary endpoint was progression-free survival (PFS). The Secondary endpoints included overall survival (OS), 6-month PFS rate, objective response rate (ORR), and disease control rate (DCR). Also, adverse events were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Results: A total of 29 patients (including 20 glioblastomas, 1 diffuse midline glioma, 5 anaplastic astrocytoma, and 3 anaplastic oligodendroglioma) were included in this study. Of these, 34.48% of the patients were treated with anlotinib alone and 65.52% with anlotinib combination therapy. The median follow-up time was 11.6 months (95% confidence interval [CI]: 9.4-15.7). The median PFS was 9.4 months (95% CI: 6.5-12.3), and the 6-month PFS rate was 62.1%. The median OS was 12.7 months (95% CI: 9.7-15.7), and the 12-month OS rate was 48.3%. Evaluation of treatment response was performed according to RANO (response assessment in neuro-oncology, RANO) criteria, including 21 partial response, 6 stable disease, and 2 PFS events. The ORR and DCR were 72.4%, and 93.1%, respectively. Grade III AEs occurred in 2 patients, and the others were less than grade III. The most common AE was thrombocytopenia, with an incidence rate of 31.0%. All AEs were alleviated and controlled by symptomatic treatment. No treatment-related deaths occurred. Conclusion: Anlotinib had a low incidence of AEs and good safety in the treatment of recurrent high-grade glioma. Moreover, it showed good short-term effectiveness and significantly prolonged the PFS of patients, which may become a promising therapeutic option for recurrent high-grade glioma and lay a foundation for further clinical studies.

Rosa Roxburghii Tratt Fruit Extract Prevents Dss-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota and the IL-17 Signaling Pathway.

Ulcerative colitis (UC) is a non-specific inflammatory bowel illness characterized by intestinal mucosal barrier degradation, inflammation, oxidative damage, and gut microbiota imbalances. Rosa roxburghii Tratt Fruit extract (RRTE) was extracted from Rosa roxburghii Tratt fruit, exhibiting an excellent prevention effect against UC; RRTE could prevent the damage of DSS-induced human normal colonic epithelial (NCM 460) cells, especially in cell viability and morphology, and oxidative damage. Additionally, in UC mice, RRTE could limit the intestinal mucosal barrier by increasing the expression of intestinal tight junction proteins and mucin, reducing inflammation and oxidative damage in colon tissue. More importantly, RRTE can increase the abundance of beneficial bacteria to regulate gut microbiota such as Ruminococcus, Turicibacter, and Parabacteroides, and reduce the abundance of harmful bacteria such as Staphylococcus and Shigella. Furthermore, transcriptomics of colonic mucosal findings point out that the beneficial effect of RRTE on UC could be attributed to the modulation of inflammatory responses such as the IL-17 and TNF signaling pathways. The qPCR results confirm that RRTE did involve the regulation of several genes in the IL-17 signaling pathway. In conclusion, RRTE could prevent DSS-induced damage both in vitro and in vivo.

Chemopreventive Effects of Polysaccharides and Flavonoids from Okra Flowers in Azomethane/Dextran Sulfate Sodium-Induced Murine Colitis-Associated Cancer.

Okra flowers are a good source of polysaccharides and flavonoids, with biological activities of anti-inflammatory action and modulation of the gut microbiota. Previously, we reported that flavonoid-rich extracts from okra flowers (AFE) presented effective anti-colorectal cancer (CRC) activity in CRC cells as well as xenograft models, but their role in colitis-associated cancer (CAC) is unidentified. In this study, we aimed to evaluate the effects of AFE and APE (polysaccharides extracted from okra flowers) on the CAC symptoms of azoxymethane (AOM)/dextran sodium sulfate (DSS)-intervened mice. The results showed that APE and AFE exert potent efficacy in inhibiting colitis and colorectal tumorigenesis stimulated by AOM/DSS, characterized by decreased colonic shortening, DAI score, and tumor numbers. Compared with the control group, APE/AFE alleviated the microbiota dysbiosis driven by AOM/DSS. In addition, AFE elicited its anticancer activity through regulation of NFκB/IL-6/Stat3, JAK2/Stat3, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in AOM/DSS mice, which was consistent with a vitro model of CT26 cells, while APE treatment exhibited anticancer activity through regulation of Nrf2/IL-6, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in the AOM/DSS mouse model. Collectively, our studies revealed, for the first time, that flavonoids and polysaccharides from okra flowers possess the ability to attenuate colitis and colorectal tumorigenesis, with them having great potential to become promising candidates against CRC.

Effects of Rosa roxburghii Tratt on Ulcerative Colitis: An Integrated Analysis of Network Pharmacology and Experimental Validation.

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein-Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway.

Blueberry Juice Attenuates Pulmonary Fibrosis via Blocking the TGF-ß1/Smad Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal, and chronic lung disease, lacking a validated and effective therapy. Blueberry has demonstrated multiple pharmacological activities including anti-inflammatory, antioxidant, and anticancer. Therefore, the objective of this study was to investigate whether blueberry juice (BBJ) could ameliorate IPF. Experiments in vitro revealed that BBJ could significantly reduce the expressions of TGF-ß1 modulated fibrotic protein, which were involved in the cascade of fibrosis in NIH/3T3 cells and human pulmonary fibroblasts. In addition, for rat primary lung fibroblasts (RPLFs), BBJ promoted the cell apoptosis along with reducing the expressions of α-SMA, vimentin, and collagen I, while increasing the E-cadherin level. Furthermore, BBJ could reverse epithelial-mesenchymal transition (EMT) phenotypic changes and inhibit cell migration, along with inducing the upregulation of E-cadherin in A549 cells. Compared with the vehicle group, BBJ treatment alleviated fibrotic pathological changes and collagen deposition in both bleomycin-induced prevention and treatment pulmonary fibrosis models. In fibrotic lung tissues, BBJ remarkably suppressed the expressions of collagen I, α-SMA, and vimentin and improved E-cadherin, which may be related to its inhibition of the TGF-ß1/Smad pathway and anti-inflammation efficacy. Taken together, these findings comprehensively proved that BBJ could effectively prevent and attenuate idiopathic pulmonary fibrosis via suppressing EMT and the TGF-ß1/Smad signaling pathway.

Anthocyanin-rich blueberry extracts and anthocyanin metabolite protocatechuic acid promote autophagy-lysosomal pathway and alleviate neurons damage in in vivo and in vitro models of Alzheimer's disease.

OBJECTIVES: As the global aging phenomenon intensifies, the incidence of Alzheimer's disease (AD) is gradually increasing. Diet appears to be an effective way to prevent and delay the progression of AD. Previous studies have found that cognitive impairment and neuronal damage were effectively alleviated by blueberry extract (BBE) in AD mice, but its mechanism is still unclear. The aims of this study were to detect the main anthocyanins of BBE; then to verify the protective effects of anthocyanin-rich BBE on hippocampal neurons and the promotion of autophagy; and finally to investigate the main protective effects and mechanisms of protocatechuic acid (PCA), a major metabolite of BBE, for promoting autophagy and thus playing a neuroprotective role. METHODS: APP/PS1 mice were given 150 mg/kg BBE daily for 16 wk. Morphology of neurons was observed and autophagy-related proteins were detected. RESULTS: Neuron damage in morphology was reduced and the expression of autophagy-related proteins in APP/PS1 mice were promoted after BBE treatment. In vitro, Aß25-35-induced cytotoxicity, including decreased neuron viability and increased levels of lactate dehydrogenase and reactive oxygen species, was effectively reversed by PCA. Furthermore, by adding autophagy inducers rapamycin and autophagy inhibitors Bafilomycin A1, it was verified that degradation of autophagosomes was upregulated and autophagy was promoted by PCA. CONCLUSION: This study elucidated the mechanism of BBE for reducing neuronal damage by promoting neuronal autophagy and proved PCA may be the main bioactive metabolite of BBE for neuroprotective effects, providing a basis for dietary intervention in AD.