PILRB potentiates the PI3K/AKT signaling pathway and reprograms cholesterol metabolism to drive gastric tumorigenesis and metastasis.

Paired immunoglobin-like type 2 receptor beta (PILRB) mainly plays a crucial role in regulating innate immunity, but whether PILRB is involved in cancer is poorly understood. Here, we report that PILRB potentiates the PI3K/AKT pathway to drive gastric tumorigenesis by binding and stabilizing IRS4, which could hyperactivate the PI3K/AKT pathway. Firstly, the levels of PILRB are upregulated in human gastric cancer (GC) specimens and associated with poor prognosis in patients with GC. In addition, our data show that PILRB promotes cell proliferation, colony formation, cell migration and invasion in GC cells in vitro and in vivo. Mechanistically, PILRB recruits the deubiquitination enzymes OTUB1 to IRS4 and relieves K48-linked ubiquitination of IRS4, protecting IRS4 protein from proteasomal-mediated degradation and subsequent activation of the PI3K/AKT pathway. Importantly, the levels of PILRB are positively correlated with IRS4 in GC specimens. Meanwhile, we also found that PILRB reprogrammed cholesterol metabolism by altering ABCA1 and SCARB1 expression levels, and PILRB-expression confers GC cell resistance to statin treatment. Taken together, our findings illustrate that the oncogenic role of PILRB in gastric tumorigenesis, providing new insights into the regulation of PI3K/AKT signaling in GC and establishing PILRB as a biomarker for simvastatin therapy resistance in GC.

[Analysis of the Occurrence and Influencing Factors of Oral Frailty in Elderly Residents of Elderly Care Facilities]. / å »è€æœºæž„è€å¹´äººå£è ”è¡°å¼±å‘ç”Ÿæƒ å†µåŠå½±å“å› ç´ åˆ†æž.

Objective: To investigate the occurrence and influencing factors of oral frailty in elderly residents of elderly care facilities and to provide a basis for the development of effective intervention programs for oral frailty in this population. Methods: A combination of subjective and objective measurements of oral frailty, a general information questionnaire, a leisure activity questionnaire, the Dietary Variety Score (DVS), the Short Nutritional Assessment Questionnaire (SNAQ), the Short-Form Mini Nutritional Assessment (MNA-SF), Barthel Index (BI), the Mini-Mental State Examination (MMSE), 15-Item Geriatric Depression Scale (GDS-15), and the Generalized Anxiety Disorder Scale-2 (GAD-2) were used to survey 348 elderly residents in three elderly care facilities in Chengdu and to analyze the factors related to oral frailty. Results: The prevalence of oral frailty in elderly residents of elderly care facilities was 31.0% (108/348). Multivariate logistic regression analysis revealed that advanced age (odds ratio [OR]=1.347, 95% confidence interval [CI]: 1.237-1.496, P<0.001), cognitive impairment (OR=6.769, 95% CI: 2.628-18.916, P<0.001), and depression (OR=8.632, 95% CI: 1.931-44.387, P=0.007) were risk factors for oral frailty in elderly residents of elderly care facilities. High scores in leisure activities (OR=0.883, 95% CI: 0.786-0.986, P=0.030), and dietary diversity (OR=0.199, 95% CI: 0.069-0.530, P=0.002) were protective factors against oral frailty. Conclusion: The prevalence of oral frailty is relatively high among elderly residents of elderly care facilities. Risk factors for oral frailty include advanced age, cognitive impairment, and depression, while increased levels of leisure activities and dietary diversity can help prevent the occurrence of oral frailty in elderly individuals.

Serum HMGB-1 released by ferroptosis and necroptosis as a novel potential biomarker for systemic lupus erythematosus.

High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of HMGB-1 in the process of SLE remains unclear. This study aims to demonstrate the potential diagnosing role of serum HMGB-1 in SLE that released by necroptosis and ferroptosis. We found that the serum levels of HMGB-1, receptor-interacting protein kinase 3 (RIPK3) /mixed lineage kinase domain-like protein (MLKL) related with necroptosis, and metabolites associated with ferroptosis were significantly upregulated in SLE patients compared to HC individuals. These serum levels were positively correlated with SLE disease activity. Additionally, the serum level of HMGB-1 showed a strong positive correlated with the levels of RIPK3/MLKL and ferroptosis metabolites. Moreover, the serum level of HMGB-1 was correlated with renal involvement and high-antinuclear antibodies (ANA) titer. After SLE serum and interferon γ (IFN-γ) treatment in vitro, the level of necroptosis and ferroptosis markers were activated and HMGB1 was released both in HEK293 and HK2 cells. Clinically, HMGB-1 was considered as a significant independent risk factor in SLE serum by binary logistic assay. Notably, HMGB-1 exhibited outstanding diagnostic ability for SLE by the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Taken together, our study indicates that the serum level of HMGB-1 is a promising biomarker for the diagnosis and monitoring of SLE.

Flaxseed polyphenols: Effects of varieties on its composition and antioxidant capacity.

This study identified phenolic compounds in five flaxseed varieties and evaluated their antioxidant activities. Results showed significant variations in phenolic acids and flavonoids among the varieties. Longya 16 had the lowest flavonoid content, Longya 13 had the lowest phenolic acid content, while Longya 10 exhibited the highest content and diversity of polyphenols, including six flavonoids (vitexin, quercitrin, quercetin, apigenin, kaempfero1, (+)-dihydroquercetin) and five phenolic acids (gallic acid, vanillic acid, ferulic acid, sinapic acid, and 4-hydroxybenzoic acid). Antioxidant activity was assessed using DPPH and ABTS radical scavenging assays, and cell-based assays under tBHP-induced oxidative stress. Flaxseed polyphenol extracts significantly reduced ROS, MDA, and GSSG levels and increased SOD and CAT activities, preserving cell vitality and morphology. These findings confirmed the significant antioxidant activity of flaxseed polyphenols, providing a theoretical basis for their application in antioxidative functional areas.

68Ga-PSMA-11 PET and mpMRI in the diagnosis of initial lymph node staging of prostate cancer: a head-to-head comparative meta-analysis.

Purpose: This meta-analysis evaluates the comparative diagnostic efficacy of 68Ga-prostate-specific membrane antigen-11 PET (68Ga-PSMA-11 PET) and multiparametric MRI (mpMRI) for the initial lymph node staging of prostate cancer. Methods: We searched PubMed and Embase databases through October 2023 for studies that provide a head-to-head comparison of 68Ga-PSMA-11 PET and mpMRI, using pelvic lymph node dissection as the gold standard. We assessed sensitivity and specificity using the DerSimonian and Laird method, with variance stabilization via the Freeman-Tukey double inverse sine transformation. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. Results: The meta-analysis incorporated 13 articles, involving a total of 1,527 patients. 68Ga-PSMA-11 PET demonstrated an overall sensitivity of 0.73 (95% CI: 0.51-0.91) and a specificity of 0.94 (95% CI: 0.88-0.99). In comparison, mpMRI showed a sensitivity of 0.49 (95% CI: 0.30-0.68) and a specificity of 0.94 (95% CI: 0.88-0.99). Although 68Ga-PSMA-11 PET appeared to be more sensitive than mpMRI, the differences in sensitivity (p = 0.11) and specificity (p = 0.47) were not statistically significant. Conclusion: Our findings indicated that 68Ga-PSMA-11 PET and mpMRI exhibit similar sensitivity and specificity in the diagnosis of initial lymph node staging of prostate cancer. However, given that most included studies were retrospective, further prospective studies with larger sample sizes are essential to validate these results. Systematic Review Registration: PROSPERO code is CRD42023495266.

Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years. The embryo is regarded as a semi-allogeneic graft to the mother. A successful pregnancy requires transition to an immune environment conducive to embryo survival at the maternal-fetal interface. As an important member of regulatory immunity, regulatory T (Treg) cells play a key role in regulating immune tolerance at the maternal-fetal interface. This review will focus on the phenotypic plasticity and lineage stability of Treg cells to illustrate its relationship with URSA.

The impact of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fractures.

PURPOSE: This study aims to investigate the impact of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fractures. MATERIALS AND METHODS: Patients diagnosed with definitive thoracolumbar spine fractures and underwent surgical treatment at our hospital between February 2022 and August 2023 were selected. Patients were divided into a treatment group (specialized nursing care at fracture sites coordinated with disease progression monitoring) and a control group (conventional care) based on different nursing methods. RESULTS: A comparative assessment was conducted to evaluate the role and significance of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fracture rehabilitation. The results showed that compared to conventional care, specialized nursing care at fracture sites coordinated with disease progression monitoring could better promote the recovery of patients' neurological functions, alleviate pain, and effectively improve symptoms and functional recovery, thus enhancing patients' quality of life and satisfaction. CONCLUSION: The study confirms the effectiveness of specialized nursing care at fracture sites coordinated with disease progression monitoring in clinical practice post thoracolumbar spine fractures.

A 4-year tunneled hemodialysis catheter malpositioned into the azygos vein and how to remedy the hemodialysis circuit.

Mispositioning in the azygos vein is a rare but hazardous complication of central venous catheterization. A patient was admitted for a dysfunctional hemodialysis tunneled cuffed catheter (TCC) placed in the azygos vein for 4 years. Computed tomography angiography revealed multiple sites of occlusion, including the superior vena cava (SVC), right and left innominate veins (IVs), and right femoral vein. Percutaneous transluminal angioplasty and a TCC replacement based on a segment-by-segment recanalizing strategy were performed. First, an 8-Fr sheath was inserted through the left femoral vein approach to retrogradely traverse the occlusive SVC followed by a guidewire extending to the occlusive left IV. A left transjugular 15-cm snare was inserted to capture the transfemoral guidewire and achieve recanalization from the left IV to the SVC. Second, a transjugular guidewire was advanced through the dysfunctional TCC yet shunted into the left IV due to the inability to cross the SVC. A left transfemoral 15-cm snare was inserted to capture the guidewire and achieve complete recanalization from the right internal jugular vein to the SVC. Balloons were passed over the guidewires to dilate the obstructive lesions sequentially, and a new TCC was inserted successfully with the tip positioned in the right atrium.

Stents migration into right atrium from severely calcified superior vena cava in a hemodialysis patient.

Vascular calcification is common among hemodialysis patients. In this report, we presented a case of superior vena cava (SVC) stent migration during endovascular angioplasty in a 50-year-old female hemodialysis patient with severe SVC calcification. The stent migration was refractory to the deployment of a second anchor stent, which shortly resulted in pericardium tamponade and was successfully rescued by emergent thoracotomy. The potential role of vascular calcification as a risk factor to stent migration was discussed. Patients with severe vascular calcification receiving endovascular angioplasty might need a careful risk screening for stent migration.

Reinsertion of tunneled-cuffed catheter in hemodialysis patients with catheter loss and limited access options.

PURPOSE: Maintenance hemodialysis patients who rely on tunneled-cuffed catheters (TCCs) often face difficulty in reinserting a new catheter when the original catheter has been extruded or removed. Potential pathological changes of vessel caused by long-term indwelling of a catheter may contribute to this predicament. The aim of this study was to report and evaluate a re-catheterization technique through the same exit site and tunnel for hemodialysis patients with TCC loss. METHODS: A retrospective review of 19 patients with TCC loss was conducted from January 2020 to August 2022. These patients underwent reinsertion through the same exit site and subcutaneous existing tunnel. Procedure-related complications and clinical follow-up data were collected. RESULTS: All 19 patients with catheter loss underwent this procedure and the median duration of catheter loss was 14 days (5-57 days). Five of them had central venous occlusion, and four of them experienced catheter loss due to removal for catheter-related bloodstream infections (CRBI). In the end, 18 case received successful catheterization using this technique. The most common complication was minimal bleeding after the operation. There were no procedure-related deaths or serious complications. The average blood flow was 265.79 ± 25.89 ml/min at the end of the follow-up period. CONCLUSION: This maneuver is a safe and convenient technique that can be used to reinsert a TCC for patients with long-time catheter loss. It helps to preserve the limited central venous resources for patients who have difficulty establishing other stable vascular access.

The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.

Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's Q test and I2 statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, P = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by matrix stiffness in solid tumors and is often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors and corresponding mechanotransducers in the cytoplasm, modulating the phenotype of TAMs. Currently, tuning TAM polarization through matrix stiffness-induced mechanical stimulation has received increasing attention, whereas its effect on TAM fate has rarely been summarized. A better understanding of the relationship between matrix stiffness and macrophage function will contribute to the development of new strategies for cancer therapy. In this review, we first introduced the overall relationship between macrophage polarization and matrix stiffness, analyzed the changes in mechanoreceptors and mechanotransducers mediated by matrix stiffness on macrophage function and tumor progression, and finally summarized the effects of targeting ECM stiffness on tumor prognosis to provide insight into this new field.

Risk factors for hypotension in patients with hemodialysis-associated superior vena cava syndrome.

OBJECTIVE: We analyzed the risk factors for hypotension in patients with hemodialysis-associated superior vena cava syndrome (SVCS) and effectiveness of endovascular intervention in hypotension related to SVCS. METHODS: This was a retrospective cohort study. A total of 194 maintenance hemodialysis patients diagnosed with SVCS who were admitted to the Department of Nephrology, West China Hospital of Sichuan University from January 2019 to December 2021 were selected and divided into a hypotension group and a nonhypotension group. Demographic and clinical data were compared. Hypotension simply refers to blood pressure levels of <90/60 mm Hg on a nondialysis day. All patients received endovascular intervention. RESULTS: Hypotension was found in 85 of the 194 patients. The following factors were significantly different between the hypotension and nonhypotension groups: body mass index, history of hypertension, tunneled-cuffed catheter as the means of dialysis access, azygos ectasis, SVC stenosis of >70% or occlusion, occlusion at the cavitary junction, serum calcium, diastolic left ventricular (LV) posterior wall thickness, LV end-diastolic volume, stroke output, and LV ejection fraction. Multivariate logistic regression analysis showed that hypertension history (OR, 0.314; P = .027), tunneled-cuffed catheter as vascular access (OR, 3.997; P < .001), SVC stenosis of >70% or occlusion (OR, 5.243; P < .001), LV posterior wall thickness (OR, 0.772; P = .044), and serum calcium (OR, 0.146; P = .005) were independent risk factors for hypotension. The mean values of systolic and diastolic blood pressure after intravascular treatment were significantly elevated from those before intervention (P < .001). The primary patency rates of SVC were 66.8%, 58.7%, and 50.0% at 3, 6, and 12 months after the procedure. CONCLUSIONS: The incidence of hypotension in patients with hemodialysis-associated SVCS is high. The identification of risk factors of hemodialysis-related hypotension provides insight into potential treatment strategies. Endovascular treatment is expected to improve hypotension related to SVCS in hemodialysis patients.

Development of a monoclonal antibody-based lateral flow immunoassay for the detection of benzoic acid in liquid food.

To monitor benzoic acid (BA) residues in liquid food samples, a monoclonal antibody (mAb)-based lateral flow immunoassay (LFA) was developed in this study. First, 2-aminobenzoic acid (2-AA), 3-aminobenzoic acid (3-AA), and 4-aminobenzoic acid (4-AA) were conjugated to BSA and used as immunogens. After cell fusion, mAb 6D8 from 4-AA-BSA performed best with an IC50 value of 0.21 mg L-1 using 3-AA-OVA as a heterogeneous antigen, which represented a 3.4-fold improvement compared with the homogeneous antigen 4-AA-BSA. Subsequently, eight kinds of CGNPs with sizes varying from 20.94 nm to 90.00 nm were synthesized for screening the suitable size to develop a sensitive LFA. Finally, a sensitive LFA based on colloidal gold (23.27 nm) nanoparticles was developed for screening BA with a cut-off value of 4 mg L-1, which could meet the requirement of BA detection in milk, Fanta, Sprite, Coca-Cola, and Smart samples.

Identification of a potential prognostic model combining pyroptosis-related gene with immune microenvironment for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal tumor with grave prognosis. Pyroptosis, a programmed cell death, is involved in tumorigenesis. However, a few studies have elucidated the functions of pyroptosis in PDAC. METHODS: The mRNA expression profiles were downloaded from the TCGA and GEO databases. Univariate and LASSO Cox regression analyses were used to screen out differentially expressed genes (DEGs) and construct the pyroptosis-related genes (PRGs) risk model. The efficiency of model was examined by Kaplan-Meier curve, ROC curve, and nomogram. Univariate and multivariate Cox regression analyses were utilized to assess whether the risk model could be used as an independent prognostic factor. The biological function was analyzed by GO, KEGG, and GSEA enrichment analysis. qRT-PCR and immunohistochemical staining detected gene expression. RESULTS: Totally 9 PRGs with differential expression were identified between normal and PDAC tissues. Then, according to PRGs, we filtered out three key DEGs and constructed the prognostic risk model. Kaplan-Meier curve, ROC curve, and nomogram indicated that the prognostic risk model had high survival prediction efficiency. Meanwhile, the risk model had also shown to be an independent prognostic factor. Further functional enrichment analysis showed that cell adhesion, PI3K-AKT signaling pathway, and dysregulated immune status may be associated with PDAC development. External validation of the model was carried out in the GEO cohort, and the results were similar to that in the TCGA cohort. Finally, the expression of three genes was verified by qRT-PCR and immunohistochemical staining. CONCLUSION: The prognostic risk model established in this study can give a good prediction of the prognosis of PDAC patients, which might provide insights into clinical treatments and prognostic prediction of PDAC.

GABA Application Enhances Drought Stress Tolerance in Wheat Seedlings (Triticum aestivum L.).

In this study, the effects of γ-aminobutyric acid (GABA) on physio-biochemical metabolism, phenolic acid accumulation, and antioxidant system enhancement in germinated wheat under drought stress was investigated. The results showed that exogenous GABA reduced the oxidative damage in wheat seedlings caused by drought stress and enhanced the content of phenolics, with 1.0 mM being the most effective concentration. Six phenolic acids were detected in bound form, including p-hydroxybenzoic acid, vanillic acid, syringic acid, p-coumaric acid, ferulic acid, and sinapic acid. However, only syringic acid and p-coumaric acid were found in free form. A total of 1.0 mM of GABA enhanced the content of total phenolic acids by 28% and 22%, respectively, compared with that of drought stress, on day four and day six of germination. The activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) were activated by drought stress plus GABA treatment. Antioxidant enzyme activities were also induced. These results indicate that GABA treatment may be an effective way to relieve drought stress as it activates the antioxidant system of plants by inducing the accumulation of phenolics and the increase in antioxidant enzyme activity.

Cuproptosis-related miRNAs signature and immune infiltration characteristics in colorectal cancer.

BACKGROUND: A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported. METHODS: miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis-related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis. RESULTS: Six cuproptosis-related miRNAs (hsa-miR-653, hsa-miR-216a, hsa-miR-3684, hsa-miR-4437, hsa-miR-641, and hsa-miR-552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129-1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal-activated genes, and stromal score was higher in the high-risk group. The IPS analysis showed a better response to immunotherapy in the low-risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR-653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR-653 predicted a shorter overall survival (p = 0.0282) and disease-free survival (p = 0.0056). In addition, miR-653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3'-UTR of DLD mRNA. CONCLUSION: We constructed a cuproptosis-related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR-653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD.

NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression.

Although the patient's survival time in various cancers has significantly increased in recent decades, the overall 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) has remained virtually unchanged due to rapid progression and metastasis. While N-acetyltransferase 10 (NAT10) has been identified as a regulator of mRNA acetylation in many malignancies, its role in PDAC remains unclear. Here, we found that NAT10 mRNA and protein levels were upregulated in PDAC tissues. Increased NAT10 protein expression was significantly correlated with poor prognosis in PDAC patients. Through our experiments, we demonstrated that NAT10 acted as an oncogene to promote PDAC tumorigenesis and metastasis in vitro and in vivo. Mechanistically, NAT10 exerts its oncogenic effects by promoting mRNA stability of receptor tyrosine kinase AXL in an ac4C-dependent manner leading to increased AXL expression and further promoting PDAC cell proliferation and metastasis. Together, our findings highlight the critical of NAT10 in PDAC progression and reveal a novel epigenetic mechanism by which modified mRNA acetylation promotes PDAC metastasis.

(-)-Epigallocatechin-3-Gallate Attenuates the Adverse Reactions Triggered by Selenium Nanoparticles without Compromising Their Suppressing Effect on Peritoneal Carcinomatosis in Mice Bearing Hepatocarcinoma 22 Cells.

Increasing evidence shows that selenium and polyphenols are two types of the most reported compounds in tumor chemoprevention due to their remarkable antitumor activity and high safety profile. The cross-talk between polyphenols and selenium is a hot research topic, and the combination of polyphenols and selenium is a valuable strategy for fighting cancer. The current work investigated the combination anti-peritoneal carcinomatosis (PC) effect of selenium nanoparticles (SeNPs) and green tea (Camellia sinensis) polyphenol (-)-epigallocatechin-3-gallate (EGCG) in mice bearing murine hepatocarcinoma 22 (H22) cells. Results showed that SeNPs alone significantly inhibited cancer cell proliferation and extended the survival time of mice bearing H22 cells. Still, the potential therapeutic efficacy is accompanied by an approximately eighty percent diarrhea rate. When EGCG was combined with SeNPs, EGCG did not affect the tumor proliferation inhibition effect but eliminated diarrhea triggered by SeNPs. In addition, both the intracellular selectively accumulated EGCG without killing effect on cancer cells and the enhanced antioxidant enzyme levels in ascites after EGCG was delivered alone by intraperitoneal injection indicated that H22 cells were insensitive to EGCG. Moreover, EGCG could prevent SeNP-caused systemic oxidative damage by enhancing serum superoxide dismutase, glutathione, and glutathione peroxidase levels in healthy mice. Overall, we found that H22 cells are insensitive to EGCG, but combining EGCG with SeNPs could protect against SeNP-triggered diarrhea without compromising the suppressing efficacy of SeNPs on PC in mice bearing H22 cells and attenuate SeNP-caused systemic toxicity in healthy mice. These results suggest that EGCG could be employed as a promising candidate for preventing the adverse reactions of chemotherapy including chemotherapy-induced diarrhea and systemic toxicity in cancer individuals.

Antioxidant, antihyperglycemic, and antihyperlipidemic properties of Chimonanthus salicifolius S. Y. Hu leaves in experimental animals: modulation of thioredoxin and glutathione systems, renal water reabsorption, and gut microbiota.

Introduction: Excessive calorie intake and physical inactivity have dramatically increased nutrient overload-associated disease, becoming a global public health issue. Chimonanthus salicifolius S. Y. Hu (CHI) is a homology plant of food and medicine in China and shows several health benefits. Methods: This work investigated the antioxidant activity, the alleviating effects, and the mechanism of action on diabetes and hyperlipidemia of CHI leaves. Results and discussion: Results showed that CHI leaves infusion displayed in vitro antioxidant activity measured by ABTS and ferric reducing antioxidant power methods. In wild-type Kunming mice, CHI leaves infusion consumption activated the hepatic antioxidant enzymes, including glutathione reductase, glutathione S-transferase, glutathione peroxidase and thioredoxin reductase as well as thioredoxin reductase 1. In alloxan-induced type 1 diabetic mice, CHI leaves infusion ameliorated diabetic symptoms, including polyuria, polydipsia, polyphagia and hyperglycemia, in a dose-dependent and time-course manners. The mechanism involved CHI leaves up-regulating renal water reabsorption associated protein - urine transporter A1-and promoting the trafficking of urine transporter A1 and aquaporin 2 to the apical plasma membrane. Despite this, in high-fat diet-induced hyperlipidemic golden hamsters, CHI leaves powder did not significantly effect on hyperlipidemia and body weight gain. This might be attributed to CHI leaves powder increasing the calorie intake. Interestingly, we found that CHI leaves extract containing a lower dose of total flavonoid than CHI leaves powder pronouncedly reduced the levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum in golden hamsters fed a high-fat diet. Furthermore, CHI leaves extract elevated the diversity of gut microbiota and the abundance of Bifidobacterium and Ruminococcaceae_UCG-014. It also decreased the abundance of Lactobacillus at the genus level in golden hamsters fed a high-fat diet. Overall, CHI leaves benefit oxidative stress prevention and metabolic syndrome amelioration in vivo.