TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.

ANOS1 accelerates the progression of esophageal cancer identified by multi-omic approaches.

To assess the role of ANOS1 in esophageal cancer (ESCA) progression, multi-omic analysis and experimental validation were employed. It was revealed that ANOS1 expression is significantly enhanced in ESCA patients and cell lines. The expression level of ANOS1 in ESCA patients can distinguish the malignancy from normal tissue with an area under curve (AUC) >0.75. Moreover, increased expression of ANOS1 is associated with advanced T stage and worse disease-free survival of ESCA patients. Therefore, a clinically applicable nomogram with ANOS1 was established with strong predictive power. Furthermore, high expression of ANOS1 in ESCA is correlated with (i) the enrichment of epithelial-mesenchymal transition by gene set enrichment analysis, (ii) the involvement in hypoxia, angiogenesis, WNT signaling pathway, and TGFß signaling pathway by gene set variation analysis, (iii) the presence of the small insertion and deletion mutational signature ID9, associated with chromothripsis, in the single-nucleotide polymorphism analysis, (iv) the amplification of 11q13.3 in the copy number variants analysis, (v) the enrichment of cancer-associated fibroblasts and mesenchymal stromal cells in the tumor microenvironment. All the results from multi-omic analysis indicate that ANOS1 plays a pivotal role in accelerating the progression of ESCA. Results from in vivo and in vitro experiments show that the knockdown of ANOS1 hampers the proliferation of ESCA cells, further validating the oncogenic role of ANOS1 in ESCA. Additionally, potential chemotherapeutics with sensitivity were identified in the high-ANOS1 group. In conclusion, ANOS1 accelerates the progression of ESCA.

Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections.

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.

Current-induced domain wall motion in a van der Waals ferromagnet Fe3GeTe2.

The manipulation of spin textures by spin currents is of fundamental and technological interest. A particularly interesting system is the 2D van der Waals ferromagnet Fe3GeTe2, in which Néel-type skyrmions have recently been observed. The origin of these chiral spin textures is of considerable interest. Recently, it was proposed that these derive from defects in the structure that lower the symmetry and allow for a bulk vector Dzyaloshinsky-Moriya interaction. Here, we demonstrate current-induced domain wall motion in Fe3GeTe2 flakes, in which the maximum domain wall velocity is an order of magnitude higher than those reported in previous studies. In heterostructures with Pt or W layers on top of the Fe3GeTe2 flakes, domain walls can be moved via a combination of spin transfer and spin-orbit torques. The competition between these torques leads to a change in the direction of domain wall motion with increasing magnitude of the injected current.

A low noise capacitance to voltage readout circuit based on active feedback charge sensitive amplifier for micro-gyro.

Trans-impedance amplifier (TIA) based capacitance-voltage (C-V) readout circuits are widely used in micro-machined gyroscopes' control system. In this work, the noise performance of a TIA and charge sensitive amplifier (CSA) based C-V readout circuit is analyzed in detail. The theoretical derivation and simulation experiments carried out in this paper show that the thermal noise of high value feedback resistors in TIA dominates the output noise of the circuit, while a CSA-based readout circuit can overcome this shortcoming. Then, a CSA-based C-V readout circuit is designed with a 1.8 V transistor on a 180 nm complementary metal-oxide-semiconductor. This C-V-based readout circuit occupies an area of 0.039 mm2, which is smaller than the area of a 0603 package resistor. When 1 V bias voltage (Vb) is added to the capacitors under test, the tested C-V gain of this circuit is as high as 225 dB, and the tested output noise of the circuit is less than 150 nV/Hz. Finally, the fabricated chip achieved a resolution of 840 zF/Hz at Vb as low as 1 V. This CSA-based C-V readout circuit has more advantages in terms of noise and area over the TIA circuit and is more suitable for integration into the interface integrated circuit for micro-gyroscopes.

Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy.

OBJECTIVE: This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS: A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS: A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION: This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

Genetic Evidence for a Causal Relationship Between Innate Leukocytes and the Risk of Digestive System Cancers in East Asians and Europeans.

Background: Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Methods: Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Results: Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Conclusions: Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

Effect of bolus materials on dose deposition in deep tissues during electron beam radiotherapy.

Several materials are utilized in the production of bolus, which is essential for superficial tumor radiotherapy. This research aimed to compare the variations in dose deposition in deep tissues during electron beam radiotherapy when employing different bolus materials. Specifically, the study developed general superficial tumor models (S-T models) and postoperative breast cancer models (P-B models). Each model comprised a bolus made of water, polylactic acid (PLA), polystyrene, silica-gel or glycerol. Geant4 was employed to simulate the transportation of electron beams within the studied models, enabling the acquisition of dose distributions along the central axis of the field. A comparison was conducted to assess the dose distributions in deep tissues. In regions where the percentage depth dose (PDD) decreases rapidly, the relative doses (RDs) in the S-T models with silica-gel bolus exhibited the highest values. Subsequently, RDs for PLA, glycerol and polystyrene boluses followed in descending order. Notably, the RDs for glycerol and polystyrene boluses were consistently below 1. Within the P-B models, RDs for all four bolus materials are consistently below 1. Among them, the smallest RDs are observed with the glycerol bolus, followed by silica-gel, PLA and polystyrene bolus in ascending order. As PDDs are ~1-3% or smaller, the differences in RDs diminish rapidly until are only around 10%. For the S-T and P-B models, polystyrene and glycerol are the most suitable bolus materials, respectively. The choice of appropriate bolus materials, tailored to the specific treatment scenario, holds significant importance in safeguarding deep tissues during radiotherapy.

Cross-talk between disulfidptosis and immune check point genes defines the tumor microenvironment for the prediction of prognosis and immunotherapies in glioblastoma.

Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.

X-ray-downregulated nucleophosmin induces abnormal polarization by anchoring to G-actin.

Ionizing radiation poses significant risks to astronauts during deep space exploration. This study investigates the impact of radiation on nucleophosmin (NPM), a protein involved in DNA repair, cell cycle regulation, and proliferation. Using X-rays, a common space radiation, we found that radiation suppresses NPM expression. Knockdown of NPM increases DNA damage after irradiation, disrupts cell cycle distribution and enhances cellular radiosensitivity. Additionally, NPM interacts with globular actin (G-actin), affecting its translocation and centrosome binding during mitosis. These findings provide insights into the role of NPM in cellular processes in responding to radiation. This article enhances our comprehension of radiation-induced genomic instability and provides a foundational platform for prospective investigations within the realm of space radiation and its implications for cancer therapy.

Multienzyme Active Manganese Oxide Alleviates Acute Liver Injury by Mimicking Redox Regulatory System and Inhibiting Ferroptosis.

Drug-induced liver injury (DILI) is a severe condition characterized by impaired liver function and the excessive activation of ferroptosis. Unfortunately, there are limited options currently available for preventing or treating DILI. In this study, MnO2 nanoflowers (MnO2Nfs) with remarkable capabilities of mimicking essential antioxidant enzymes, including catalase, superoxide dismutase (SOD), and glutathione peroxidase are successfully synthesized, and SOD is the dominant enzyme among them by density functional theory. Notably, MnO2Nfs demonstrate high efficiency in effectively eliminating diverse reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide anion (O2 •-), and hydroxyl radical (•OH). Through in vitro experiments, it is demonstrated that MnO2Nfs significantly enhance the recovery of intracellular glutathione content, acting as a potent inhibitor of ferroptosis even in the presence of ferroptosis activators. Moreover, MnO2Nfs exhibit excellent liver accumulation properties, providing robust protection against oxidative damage. Specifically, they attenuate acetaminophen-induced ferroptosis by inhibiting ferritinophagy and activating the P62-NRF2-GPX4 antioxidation signaling pathways. These findings highlight the remarkable ROS scavenging ability of MnO2Nfs and hold great promise as an innovative and potential clinical therapy for DILI and other ROS-related liver diseases.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

PYCR2, induced by c-Myc, promotes the invasiveness and metastasis of breast cancer by activating AKT signalling pathway.

BACKGROUND: Pyrroline-5-carboxylate reductase 2 (PYCR2) expression is aberrantly upregulated in colon cancer. However, the functions and underlying mechanisms of PYCR2 in breast cancer remain elusive. The primary objective of the present study was to elucidate the function of PYCR2 in breast cancer and investigate whether PYCR2 may be transcriptionally regulated by c-Myc to activate the AKT signaling pathway. METHODS: Immunohistochemical analysis was performed to examine the expression of PYCR2 in breast cancer and adjacent non-cancerous tissues. Western blot and RT-qPCR were utilized to detect PYCR2 expression in breast cancer cells. Cellular functionalities were evaluated through Transwell assays in vitro and lung metastasis formation assays in vivo. Moreover, the impact of PYCR2 on the activation of AKT signaling was determined through western blot and immunohistochemistry analysis. The transcriptional regulation of PYCR2 expression by c-Myc was evaluated via both western blot analysis and luciferase gene reporter assay. RESULTS: PYCR2 overexpression was noted in breast cancer. Silencing PYCR2 expression attenuated the invasive and metastatic abilities of breast cancer cells. Furthermore, the activation of the AKT signaling pathway is indispensable for the promotion of invasion and metastasis mediated by PYCR2. Lastly, the binding of c-Myc to the promoter sequence of PYCR2 resulted in the upregulation of PYCR2 transcription. CONCLUSION: Taken together, these results indicate that PYCR2 is transcriptionally regulated by c-Myc and promotes invasion and metastasis in breast cancer through the activation of the AKT pathway.

Coarse- and Fine-Grained Fusion Hierarchical Network for Hole Filling in View Synthesis.

Depth image-based rendering (DIBR) techniques play an essential role in free-viewpoint videos (FVVs), which generate the virtual views from a reference 2D texture video and its associated depth information. However, the background regions occluded by the foreground in the reference view will be exposed in the synthesized view, resulting in obvious irregular holes in the synthesized view. To this end, this paper proposes a novel coarse and fine-grained fusion hierarchical network (CFFHNet) for hole filling, which fills the irregular holes produced by view synthesis using the spatial contextual correlations between the visible and hole regions. CFFHNet adopts recurrent calculation to learn the spatial contextual correlation, while the hierarchical structure and attention mechanism are introduced to guide the fine-grained fusion of cross-scale contextual features. To promote texture generation while maintaining fidelity, we equip CFFHNet with a two-stage framework involving an inference sub-network to generate the coarse synthetic result and a refinement sub-network for refinement. Meanwhile, to make the learned hole-filling model better adaptable and robust to the "foreground penetration" distortion, we trained CFFHNet by generating a batch of training samples by adding irregular holes to the foreground and background connection regions of high-quality images. Extensive experiments show the superiority of our CFFHNet over the current state-of-the-art DIBR methods. The source code will be available at https://github.com/wgc-vsfm/view-synthesis-CFFHNet.

Effects and mechanisms of nutritional interventions on extradigestive complications in obese patients.

BACKGROUND: Obesity is associated with an increased risk of multiple extradigestive complications. Thus, understanding the global epidemiology of obesity and its relationship with extradigestive complications, such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease is important. However, nutritional intervention can positively manage issues associated with obesity. Hence, the identification of the current high prevalence of extradigestive complications among patients with obesity and the potential role of nutritional interventions is also essential. AIM: To determine the relationship between obesity and extradigestive complications and emphasize the importance of nutritional interventions in the management of patients with obesity. METHODS: Overall, 110 patients with obesity admitted to our hospital from February 2020 to November 2022 and 100 healthy individuals were included in the present study. Information of the study population, including demographic characteristics, such as age, sex, body mass index, indicators of extradigestive complications, dietary intake, and biomarkers was collected. The study design, participant selection, interventions, and development of the nutritional intervention program were described. The collected data were analyzed to assess the effect of nutritional interventions on extradigestive complications. RESULTS: As a part of nutritional intervention, the dietary structure was modified to decrease the saturated fatty acid and cholesterol intake and increase the dietary fiber and polyunsaturated fatty acid intake to improve the blood lipid levels and cardiovascular health. Mechanistic studies showed that these nutritional interventions positively affected mechanisms that regulate lipid metabolism, improved inflammatory markers in the blood, and improved vascular functions. CONCLUSION: The study discusses the consistency of the present results with previous findings to assess the clinical significance of the present findings. The study provides direction for future research on improving nutritional intervention strategies.

Inverse association between isoflavones and prediabetes risk: evidence from NHANES 2007-2010 and 2017-2018.

Introduction: Prediabetes is a metabolic condition characterized by blood glucose levels that are higher than normal but do not meet the threshold for a diabetes diagnosis. Individuals with prediabetes are at an increased risk of developing type 2 diabetes and associated complications. However, limited epidemiological studies have investigated the association between flavonoids from plant-based diets and the risk of prediabetes, and the existing evidence from these studies is inconsistent. Methods: Therefore, we utilized data from 19,021 participants (mean age: 32.03 years) in the National Health and Nutrition Examination Survey (NHANES) conducted during 2007-2010 and 2017-2018 to investigate the potential association between dietary flavonoid intake and prediabetes risk by weighted logistic regression analysis. Furthermore, the data from 3,706 participants (mean age: 35.98 years) from NHANES 2007-2010 were used to assess the correlation between concentrations of isoflavones and their metabolites in urine and prediabetes risk by weighted logistic regression analysis. Results: Our findings revealed an inverse association between the intake of glycitein (OR: 0.88; 95% CI: 0.82-0.96; p = 0.003), genistein (OR: 0.98; 95% CI: 0.97-0.99; p = 0.004), daidzein (OR: 0.98; 95% CI: 0.96-0.99; p = 0.009), and total isoflavones (OR: 0.99; 95% CI: 0.98-1.00; p = 0.005) with the risk of prediabetes. Moreover, we observed an inverse association between the concentration of daidzein in urine (OR: 0.84; 95% CI: 0.73-0.96; p = 0.012) and the concentration of genistein in urine (OR:0.83; 95% CI: 0.75-0.93; p = 0.003) with the risk of prediabetes using weighted logistic regression. Conclusion: In conclusion, our findings suggest a potential protective effect of isoflavones against the development of prediabetes.

HDAC1 suppresses radiotherapy sensitivity in cervical cancer via regulating HIF-1α/VEGF signaling pathway.

Cervical cancer (CC) is the fourth most common cancer amongst females worldwide. Histone deacetylase (HDAC) 1 plays a vital role in several tumors. Nevertheless, its potential and mechanism in radiotherapy sensitivity underlying CC remains obscure. Hence, the objective of this research was to probe the potential of HDAC1 in CC radiotherapy sensitivity and its mechanism of action. The expression HDACs and survival analysis of HDAC1 were investigated based on the GEPIA database. Immunohistochemical staining was implemented to detect HDAC1 and Ki-67 expression in tumor tissues. RT-qPCR and Western blot were conducted to assess HDAC1, HIF-1α, VEGFA, along with VEGFR expressions in CC cells and tumor tissues. Cell viability, apoptosis, invasion, migration, along with cell cycle were analyzed by functional assays. Tumor-bearing nude mice model was established, and the tumor weight and volume were determined. HDAC1 was high-expressed in the tumor tissue and CC cells. In vitro, overexpression of HDAC1 suppressed radiotherapy sensitivity in C33A cells, while knockdown of HDAC1 promoted radiotherapy sensitivity in SiHa cells. In vivo, we found that HDAC1 silence hindered tumor growth and cell proliferation and promoted tumor cell apoptosis in nude mice after radiotherapy. In addition, we found that HDAC1 impacted radiotherapy sensitivity by modulating the HIF-1α/VEGF signaling pathway. In conclusion, HDAC1 suppressed the radiotherapy sensitivity of CC via regulating HIF-1α/VEGF signaling pathway, suggesting that HDAC1 may act as a crucial participant in regulating CC radiosensitivity, which may provide a novel method for treating CC.

Tryptophan alleviates lipopolysaccharide-induced liver injury and inflammation by modulating necroptosis and pyroptosis signaling pathways in piglets.

The liver plays crucial roles in material metabolism and immune response. Bacterial endotoxin can cause various liver diseases, thereby causing significant economic losses to pig industry. Tryptophan is an essential amino acid in piglets. However, whether tryptophan can alleviate liver injury and inflammation by regulating necroptosis and pyroptosis has not been clarified. This study aimed to investigate whether dietary tryptophan can alleviate lipopolysaccharide (LPS)-induced liver injury in weaned piglets. 18 weaned piglets were randomly distributed to three treatments, each with 6 replicates: (1) control; (2) LPS-challenged control; (3) LPS + 0.2% tryptophan. After feeding with control or 0.2% tryptophan-supplemented diets for 35 d, pigs were intraperitoneally injected with saline or LPS (100 mg/kg body weight). At 4 h post-injection, blood samples and liver were collected. Results indicated that tryptophan reduced alanine aminotransferase, aspartate aminotransferase, decreased the mRNA expression and protein expression of 70-kDa heat shock proteins. Moreover, tryptophan increased the mRNA expression and protein expression of claudin-1, occludin and zonula occludens and decreased hydrogen peroxide and malondialdehyde contents, and increased catalase, glutathione peroxidase and total superoxide dismutase activities and proinflammatory cytokine levels in the liver. Meanwhile, tryptophan inhibited pyroptosis-related and necroptosis-related protein expression in liver. Collectively, tryptophan could relieve liver damage, increased the antioxidant capacity and reduced inflammation by inhibiting pyroptosis and necroptosis signaling pathways.

Iron overload induces colitis by modulating ferroptosis and interfering gut microbiota in mice.

BACKGROUND: Iron plays a pivotal role in various physiological processes, including intestinal inflammation, ferroptosis, and the modulation of the gut microbiome. However, the way these factors interact with each other is unclear. METHODS: Mice models were fed with low, normal and high iron diets to assess their impacts on colitis, ferroptosis and gut microbiota. Untargeted fecal metabolomics analysis, 16S rRNA sequencing, histopathology analysis, real-time quantitative PCR and western blot were performed to analyze the differences in the intestinal inflammatory response and understanding its regulatory mechanisms between low, normal and high iron groups. RESULTS: The iron overload changed the serum iron, colon iron and fecal iron. In addition, the iron overload induced the colitis, induced the ferroptosis and altered the microbiome composition in the fecal of mice. By using untargeted fecal metabolomics analysis to screen of metabolites in the fecal, we found that different metabolomics profiles in the fecal samples between iron deficiency, normal iron and iron overload groups. The correlation analysis showed that both of iron deficiency and overload were closely related to Dubosiella. The relationship between microbial communities (e.g., Akkermansia, Alistipes, and Dubosiella) and colitis-related parameters was highly significant. Additionally, Alistipes and Bacteroides microbial communities displayed a close association with ferroptosis-related parameters. Iron overload reduced the concentration of metabolites, which exert the anti-inflammatory effects (e.g., (+)-.alpha.-tocopherol) in mice. The nucleotide metabolism, enzyme metabolism and metabolic diseases were decreased and the lipid metabolism was increased in iron deficiency and iron overload groups compared with normal iron group. CONCLUSION: Iron overload exacerbated colitis in mice by modulating ferroptosis and perturbing the gut microbiota. Iron overload-induced ferroptosis was associated with NRF2/GPX-4 signaling pathway. Specific microbial taxa and their associated metabolites were closely intertwined with both colitis and ferroptosis markers.

The associations between dietary flavonoid intake and the prevalence of diabetes mellitus: Data from the National Health and Nutrition Examination Survey 2007-2010 and 2017-2018.

Background: Diabetes mellitus (DM) is a prominent health concern worldwide, leading to the high incidence of disability and mortality and bringing in heavy healthcare and social burden. Plant-based diets are reported associated with a reduction of DM risk. Plant-based diets are rich in flavonoids, which possess properties such as scavenging free radicals and exerting both anti-inflammatory and antioxidant effects. Purpose: However, whether dietary flavonoids are associated with the prevalence of DM remains controversial. The potential reasons for contradictory epidemiological outcomes on the association between dietary flavonoids and DM prevalence have not been determined. Methods: To address these limitations, we employed data from 22,481 participants in the National Health and Nutrition Examination Survey to explore the association between the intake of flavonoids and DM prevalence by weighted Logistic regression and weighted restricted cubic splines. Results: We found that the prevalence of DM was inversely associated with the intake of total flavonoids in the second quartile [Odds Ratio (OR) 0.78 95% confidence interval (CI) (0.63, 0.97), p = 0.028], in the third quartile [0.76 (0.60, 0.97), p = 0.031], and in the fourth quartile [0.80 (0.65, 0.97), p = 0.027]. However, the p for trend was not significant [0.94 (0.88, 1.01), p = 0.096]. Moreover, the association between DM prevalence and the intake of total flavonoids was significantly influenced by race (p for interaction = 0.006). In Mexican Americans, there was a significant positive association between DM prevalence and total flavonoid intake within the third quartile [1.04 (1.02, 1.07), p = 0.003]. Total flavan-3-ol and subtotal catechin intake exhibited a non-linear U-shaped association with DM prevalence (p for non-linearity < 0.0001 and p for non-linearity < 0.0001, respectively). Compared to the first quartile of corresponding intakes, consumption within the third quartile of subtotal catechins [0.70 (0.55, 0.89), p = 0.005] and total flavan-3-ols [0.65 (0.50, 0.84), p = 0.002] was associated with a lower prevalence of DM. Conclusion: Taken together, our study may provide preliminary research evidence for personalized improvement of dietary habits to reduce the prevalence of diabetes.