Gut microbial metabolites SCFAs and chronic kidney disease.

The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.

Short-term prognostic models for severe acute kidney injury patients receiving prolonged intermittent renal replacement therapy based on machine learning.

BACKGROUND: As an effective measurement for severe acute kidney injury (AKI), the prolonged intermittent renal replacement therapy (PIRRT) received attention. Also, machine learning has advanced and been applied to medicine. This study aimed to establish short-term prognosis prediction models for severe AKI patients who received PIRRT by machine learning. METHODS: The hospitalized AKI patients who received PIRRT were assigned to this retrospective case-control study. They were grouped based on survival situation and renal recovery status. To screen the correlation, Pearson's correlation coefficient, partial ETA square, and chi-square test were applied, eight machine learning models were used for training. RESULTS: Among 493 subjects, the mortality rate was 51.93% and the kidney recovery rate was 30.43% at 30 days post-discharge, respectively. The indices related to survival were Sodium, Total protein, Lactate dehydrogenase (LDH), Phosphorus, Thrombin time, Liver cirrhosis, chronic kidney disease stage, number of vital organ injuries, and AKI stage, while Sodium, Total protein, LDH, Phosphorus, Thrombin time, Diabetes, peripherally inserted central catheter and AKI stage were selected to predict the 30-day renal recovery. Naive Bayes has a good performance in the prediction model for survival, Random Forest has a good performance in 30-day renal recovery prediction model, while for 90-day renal recovery prediction model, it's K-Nearest Neighbor. CONCLUSIONS: Machine learning can not only screen out indicators influencing prognosis of AKI patients receiving PIRRT, but also establish prediction models to optimize the risk assessment of these people. Moreover, attention should be paid to serum electrolytes to improve prognosis.

Short-term prognosis and influencing factors of patients with acute kidney injury treated with prolonged intermittent renal replacement therapy.

BACKGROUND: Studies assessing prognosis after prolonged intermittent renal replacement therapy (PIRRT) for acute kidney injury (AKI) are scarce. AIM: To assess the impact of PIRRT on AKI and factors associated with short-term prognosis. METHODS: In this retrospective nested case-control study, AKI patients administered PIRRT in Shanghai General Hospital from 01/2012 to 10/2018 were assigned to the 30-day survivor and death groups. Surviving patients were further divided into the kidney recovery and non-recovery groups at 30 and 90 days post-discharge, respectively. Propensity score matching was performed. RESULTS: Totally 576 patients were included in the non-matched study population, mortality and kidney recovery rates were 51.7% and 33.4%, respectively. After propensity score matching, there were 250 patients in each of the death and survival groups. Low PIRRT frequency (OR = 2.165, 95% CI = 1.178-3.978), infection (OR = 0.447, 95% CI = 0.251-0.795), number of damaged vital organs (OR = 0.478, 95% CI = 0.346-0.661), sodium (OR = 0.958, 95% CI = 0.928-0.988), total protein (OR = 1.047, 95% CI = 1.022-1.072), pre-dialysis thrombin time (TT; OR = 0.959, 95% CI = 0.936-0.983), pre-discharge glomerular filtration rate (GFR; OR = 1.024, 95% CI = 1.017-1.031) and admission ward [reference: renal ward; intensive care unit (OR = 0.042, 95% CI = 0.008-0.211); surgery (OR = 0.092, 95% CI = 0.018-0.465); medical (OR = 0.049, 95% C% CI = 0.009-0.259); other (OR = 0.097, 95% CI = 0.016-0.572)] independently predicted 30-day mortality. Peripherally inserted central catheter (OR = 13.970, 95% CI = 1.439-135.589), urea nitrogen (OR = 0.961, 95% CI = 0.933-0.990) and pre-discharge GFR (OR = 1.102, 95% CI = 1.067-1.137) independently predicted 30-day kidney recovery. Pre-dialysis Scr (OR = 0.997, 95% CI = 0.995-0.999), urea nitrogen (OR = 0.948, 95% CI = 0.912-0.986) and pre-discharge GFR (OR = 1.137 95% CI = 1.088-1.189) independently predicted 90-day kidney recovery. CONCLUSIONS: PIRRT improves survival and kidney function recovery in AKI patients. In patients with previous GFR ≥ 30 mL/(min-1.73 m2 ) and no prior maintenance dialysis, PIRRT at 3-5 sessions/week might be appropriate.

Pet-related Pasteurella multocida induced peritonitis in peritoneal dialysis: a case report and review of the literatures.

BACKGROUND: P. multocida (Pasteurella multocida) is animal-sourced gram-negative coccobacillus which can be transmitted to human through many animals including household pets. P. multocida induced peritoneal dialysis-related peritonitis has rarely been reported. In recent years, there has been an increase in the incidence of P. multocida induced peritoneal dialysis-related peritonitis, for the reason that patients with PD at home bred household pets. In this study, we present a case of a P. multocida induced peritoneal dialysis-related peritonitis, which is suspected to be caused through intimate contact with a household cat and we have reviewed 28 cases reported before and give suggestions for treatment and the way of prevention. CASE PRESENTATION: A 75-year-old man with end-stage renal disease (ESRD) for nearly 5 years on continuous ambulatory peritoneal dialysis (CAPD) was admitted to the nephrology department with a 1-week history of abdominal pain and a cloudy peritoneal dialysis effluent. Based on the history, physical examination and laboratory results with the findings in the peritoneal dialysis fluid, a diagnosis of peritoneal dialysis-related peritonitis was confirmed. The final culture of initial peritoneal effluent results indicated the organism was P. multocida. After a 12-day antibiotic treatment, the condition of patient was not improved. The patient was switched to ampicillin/sulbactam (3 g intravenously) twice every day and the condition was improved significantly. On further inquiring, the patient reported that he had had a cat at home and when the patient did CAPD, the cat was usually playing with the tubing or contacting the patient during CAPD. CONCLUSION: In our case and reviewed cases, P. multocida induced peritoneal dialysis-related peritonitis could be cured by proper antibiotic treatment. If individuals keep the pet away from the PD process, the infection route may be severed. P. multocida induced peritoneal dialysis-related peritonitis does not need catheter removal and exchange with hemodialysis except long-time intractable peritonitis.

Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis.

BACKGROUND: The clinical significance of stem cell therapy in the treatment of dilated cardiomyopathy remains unclear. This systemic appraisal and meta-analysis aimed to assess the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. After searching the PubMed, Embase, and Cochrane library databases until November 2017, we conducted a meta-analysis to evaluate the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. METHODS: The weighted mean difference (WMD), standard mean difference (SMD), relative risk (RR), and 95% confidence interval (CI) were summarized in this meta-analysis. Both fixed effects and random effects models were used to combine the data. Sensitivity analyses were conducted to evaluate the impact of an individual dataset on the pooled results. RESULTS: A total of eight randomized controlled trials, which involved 531 participants, met the inclusion criteria in this systematic appraisal and meta-analysis. Our meta-analysis showed that stem cell therapy improves left ventricular ejection fraction (SMD = 1.09, 95% CI 0.29 to 1.90, I2 = 92%) and reduces left ventricular end-systolic volume (SMD = - 0.36, 95% CI - 0.61 to - 0.10, I2 = 20.5%) and left ventricular end-diastolic chamber size (SMD = - 0.48, 95% CI - 0.89 to - 0.07, I2 = 64.8%) in patients with dilated cardiomyopathy. However, stem cell therapy has no effect on mortality (RR = 0.72, 95% CI 0.50 to 1.02, I2 = 30.2%) and 6-min-walk test (WMD = 51.52, 95% CI - 24.52 to 127.55, I2 = 94.8%). CONCLUSIONS: This meta-analysis suggests that stem cell therapy improves left ventricular ejection fraction and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. However, future well-designed large studies might be necessary to clarify the effect of stem cell therapy in patients with dilated cardiomyopathy.

Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure.

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1ß in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1ß levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.

Preliminary Evaluation of Virtual Touch Tissue Imaging Quantification for Differential Diagnosis of Metastatic and Nonmetastatic Cervical Lymph Nodes.

OBJECTIVES: Virtual Touch tissue imaging quantification (VTIQ; Siemens Medical Solutions, Mountain View, CA) is useful for assessing tissue hardness. This study aimed to investigate the value of VTIQ in differential diagnosis of cervical lymph nodes. METHODS: We retrospectively analyzed conventional sonograms and VTIQ images of 85 pathologically confirmed patients with superficial lymph node lesions. Conventional sonography was first performed, with 2-dimensional images described. Then VTIQ shear wave velocity (SWV) values of superficial lymph nodes were measured. With pathologic diagnosis as the reference standard, a receiver operating characteristic curve was generated to evaluate VTIQ efficacy in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes. RESULTS: Of the 85 nodes, 44 and 41 were metastatic and nonmetastatic, respectively. The latter group included 24 and 17 hematologic/lymphatic system disease and reactive hyperplastic nodes, respectively. Shear wave velocity values of metastatic nodes were significantly higher than those of their nonmetastatic counterparts (P < .001). With an area under the curve (AUC) of 0.953 and SWV cutoff of 3.27 m/s, accuracy, sensitivity, and specificity were 89.4%, 88.6%, and 90.2%, respectively, for distinguishing metastatic and nonmetastatic nodes. An AUC of 0.943 and SWV cutoff of 3.23 m/s yielded accuracy, sensitivity, and specificity of 88.2%, 88.6%, and 87.5% for differentiating metastatic from hematologic/lymphatic system disease nodes. Finally, an AUC of 0.968 and SWV cutoff of 3.27 m/s yielded accuracy, sensitivity, and specificity of 90.2%, 88.6%, and 94.1% for differentiating metastatic from reactive hyperplastic nodes. CONCLUSIONS: Virtual Touch tissue imaging quantification is efficient in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes.

Effect of the Combination of Hemodialysis and Hemoperfusion on Clearing Advanced Glycation End Products: A Prospective, Randomized, Two-Stage Crossover Trial in Patients Under Maintenance Hemodialysis.

Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF-α. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines.

Maternal dietary protein supplement confers long-term sex-specific beneficial consequences of obesity resistance and glucose tolerance to the offspring in Brandt's voles.

Maternal under- or over-nutrition not only alters neonatal body mass but also increases the risk of metabolic disorders in adulthood. Little is known about how maternal dietary protein affects offspring fitness in wild rodents. The present study was conducted to test the hypothesis that maternal dietary protein supplement has a long-term beneficial effect on offspring fitness in Brandt's vole (Lasiopodomys brandtii), a herbivorous rodent model. The vole dams were fed either a control (18% protein) or high-protein (36% protein) diet throughout pregnancy and lactation. After weaning, all offspring received a control diet till 14 weeks old. Energetic parameters, serum leptin concentration and glucose tolerance were measured. The adult offspring were fed high-fat diet for 8 weeks, and body weight and food intake were measured. No difference was observed in litter size, litter mass or pup mass before weaning. Maternal protein supplement increased body mass and the mass of reproductive organ but decreased digestibility and fat deposition and alleviated HFD-induced obesity especially in the males. Glucose tolerance was elevated in the offspring from maternal protein supplement, especially in the females. The accelerated growth may be associated with high serum leptin concentration at weaning, a state of leptin resistance, and the low digestibility may predispose obesity resistance especially in male offspring from maternal high-protein diet. These data demonstrate that maternal protein supplement confers the long-term sex-specific beneficial consequences of accelerated growth and improved obesity resistance and glucose tolerance of their offspring.

A retrospective study of palindrome symmetrical-tip catheters for chronic hemodialysis access in China.

Hemodialysis catheters remain necessary for long-term vascular access in patients for whom arteriovenous access may be problematic or impossible. Developments in catheter design have improved long-term catheter functionality, and reduced the rate of infection and complications associated with their use. This retrospective study of 284 cases of chronic catheterization in 271 patients treated between 2009 and 2011 using Tal Palindrome™ symmetrical-tip (N = 118) or Quinton™ Permcath™ step-tip (N = 166) hemodialysis catheters evaluates the efficacy and the safety of symmetrical-tip dialysis catheters for chronic hemodialysis, compared with a step-tip catheter. Measurements of catheter performance included mean catheter dwell time, incidence of low blood flow, and rates of infection and catheter-related blood stream infection (CRBSI). The symmetrical-tip catheter had a significantly longer mean dwell time compared with the step-tip catheter; 329.4 ± 38.1 versus 273.1 ± 25.4 d (p < 0.05). In addition, the rate of occurrence of low blood flow per 1000 catheter days was lower for the symmetrical-tip compared with the step-tip catheter; 1.13 versus 6.86 (p < 0.01). The symmetrical-tip catheter was also associated with a lower incidence of complications; the rates of infection (0.28 vs. 0.78; p < 0.01) and CRBSI (0.15 vs. 0.44; p < 0.01) were lower compared with those for step-tip catheters, and catheter removal occurred less often for the symmetrical-tip catheter (8% vs. 16%; p < 0.05). The symmetrical-tip hemodialysis catheter was associated with a longer mean dwell time, lower incidence of low blood flow, and lower infection rate compared with the step-tip catheter.

Vascular calcification in chronic kidney disease is induced by bone morphogenetic protein-2 via a mechanism involving the Wnt/ß-catenin pathway.

BACKGROUND: Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD). Phosphate is an important regulator of VC. METHODS: The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of ß-catenin was performed to examine the involvement of Wnt/ß-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. RESULTS: BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of ß-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of ß-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. CONCLUSIONS: BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/ß-catenin pathway.

Therapeutic effects of Kangxian Yanshen formula on patients with chronic kidney disease stages 3-4: a retrospective cohort study.

Background: This study retrospectively evaluated the actual efficacy of Kangxian Yanshen Formula Chinese medicine on renal function-related indicators in chronic kidney disease (CKD) stage 3-4 patients. Methods: In this retrospective cohort study, we collected 212 adult CKD patients with baseline estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2. All participants received usual care (i.e., Western medications), and participants in the exposure group (n = 109) were additionally prescribed Kangxian Yanshen Formula Chinese medicine. The primary outcome was an adjusted hazard risk and 95% confidence interval (95% CI) of a 30% decrease in eGFR at month 36 from baseline. Results: In terms of eGFR, among participants treated with additional Kangxian Yanshen Formula, after adjusting for covariates, there was a 57.1% reduction in the risk of a 30% decline from baseline in eGFR among participants in the Kangxian Yanshen Formula group compared with the Western medicine group (adjusted hazard risk: 0.429; 95% CI 0.269-0.682). In addition, participants in the Kangxian Yanshen Formula group had a significantly higher change in eGFR from baseline to month 12 than those in the western medicine group (3.40 ± 11.62 versus -3.87 ± 8.39; between-group difference Δ5.61 [± 2.26 standard deviation] mL/min/1.73 m2; P = 0.014). Participants in both groups showed a decreasing trend in eGFR at months 24 and 36. Conclusion: In patients with stage 3-4 CKD, Kangxian Yanshen Formula Chinese medicine therapy may help delay eGFR decline, but high-quality randomized controlled trials are needed to validate the results further.

Engineering Magnetic Extracellular Vesicles Mimetics for Enhanced Targeting Chemodynamic Therapy to Overcome Ovary Cancer.

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H2O2 into lethal hydroxyl radicals (•OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and ß-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H2O2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H2O2 into •OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.

Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.

OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis. METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting. RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC. CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

Inhibition of melanoma using a nanoceria-based prolonged oxygen-generating phototherapy hydrogel.

Tumor hypoxic environment is an inevitable obstacle for photodynamic therapy (PDT) of melanoma. Herein, a multifunctional oxygen-generating hydrogel loaded with hyaluronic acid-chlorin e6 modified nanoceria and calcium peroxide (Gel-HCeC-CaO2) was developed for the phototherapy of melanoma. The thermo-sensitive hydrogel could act as a sustained drug delivery system to accumulate photosensitizers (chlorin e6, Ce6) around the tumor, followed by cellular uptake mediated by nanocarrier and hyaluronic acid (HA) targeting. The moderate sustained oxygen generation in the hydrogel was produced by the reaction of calcium peroxide (CaO2) with infiltrated H2O in the presence of catalase mimetic nanoceria. The developed Gel-HCeC-CaO2 could efficiently alleviate the hypoxia microenvironment of tumors as indicated by the expression of hypoxia-inducible factor -1α (HIF-1α), meeting the "once injection, repeat irradiation" strategy and enhanced PDT efficacy. The prolonged oxygen-generating phototherapy hydrogel system provided a new strategy for tumor hypoxia alleviation and PDT.

Impact of the degree of worsening renal function and B-type natriuretic peptide on the prognosis of patients with acute heart failure.

Background: The impact of the degree of worsening renal function (WRF) and B-type natriuretic peptide (BNP) on the prognosis of patients with acute heart failure (AHF) is still debatable. The present study investigated the influence of different degrees of WRF and BNP levels at discharge on 1-year all-cause mortality in AHF. Methods: Hospitalized AHF patients diagnosed with acute new-onset/worsening of chronic heart failure (HF) between January 2015 and December 2019 were included in this study. Patients were assigned into high and low BNP groups based on the median BNP level at discharge (464 pg/ml). According to serum creatinine (Scr) levels, WRF was divided into non-severe WRF (nsWRF) (Scr increased ≥0.3 mg/dl and <0.5 mg/dl) and severe WRF (sWRF) (Scr increased ≥0.5 mg/dl); non-WRF (nWRF) was defined as Scr increased of <0.3 mg/dl). Multivariable cox regression was used to evaluate the association of low BNP value and different degrees of WRF with a all-cause death, as well as testing for an interaction between the two. Results: Among 440 patients in the high BNP group, there was a significant difference in WRF on mortality (nWRF vs. nsWRF vs. sWRF: 22% vs. 23.8% vs. 58.8%, P < 0.001). Yet, mortality did not significantly differ across the WRF subgroups in the low BNP group (nWRF vs. nsWRF vs. sWRF: 9.1% vs. 6.1% vs. 15.2%, P = 0.489). In multivariate Cox regression analysis, low BNP group at discharge (HR, 0.265; 95%CI, 0.162-0.434; P < 0.001) and sWRF (HR, 2.838; 95%CI, 1.756-4.589; P < 0.001) were independent predictors of 1-year mortality in AHF.There was a significant interaction between low BNP group and sWRF(HR, 0.225; 95%CI, 0.055-0.918; P < 0.05). Conclusions: nsWRF does not increase the 1-year mortality in AHF patients, whereas sWRF does. A low BNP value at discharge is associated with better long-term outcomes and mitigates the adverse effects of sWRF on prognosis.

Heat treatment effect on whey protein-epigallocatechin gallate interaction: A fluorescence spectroscopic analysis.

This study aimed to examine the interaction mechanism of polyphenol protein in a heat-treated aqueous solution system using epigallocatechin gallate (EGCG) and whey protein (WP) as raw materials. Further, we hypothesized the binding characteristics of these two compounds. The results were as follows: The quenching mechanism between WP and EGCG was characterized as static quenching. As the temperature increased, the binding constant and the binding force between EGCG and WP both increased. The number of binding sites (denoted as n) between WP and EGCG was approximately 1. Hence, WP provided a single site to bind to EGCG to form a complex. The main binding modes between WP and EGCG were hydrophobic and electrostatic interactions, and they were spontaneously combined into complexes (ΔG < 0). This study provided a basis for the interaction between WP and EGCG under different heating conditions and their combination mode.

Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma.

BACKGROUND: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined. METHODS: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments. RESULTS: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination. CONCLUSION: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.

Screening of pesticides in serum, urine and cerebrospinal fluid collected from an urban population in China.

Human exposure to pesticides is a topic of public health concern for decades. Pesticide exposures have been assessed through the analysis of urine or blood matrices, but little is known on the accumulation of these chemicals in cerebrospinal fluid (CSF). CSF plays an important role in maintaining physical and chemical balance of the brain and central nervous system and any perturbation can have adverse effects on health. In this study, we investigated the occurrence of 222 pesticides in CSF from 91 individuals using gas chromatography-tandem mass spectrometry (GC-MS/MS). Measured pesticide concentrations in CSF were compared with those in 100 serum and urine specimens from individuals living in the same urban location. Twenty pesticides were found in CSF, serum and urine, at levels above the limit of detection. Three most frequently detected pesticides in CSF were biphenyl (100%), diphenylamine (75%), and hexachlorobenzene (63%). Median concentrations of biphenyl in CSF, serum and urine were 1.11, 10.6, and 1.10 ng/mL, respectively. Six triazole fungicides were found only in CSF, but not in other matrices. To our knowledge, this is the first study to report pesticide concentrations in CSF in a general urban population.

ATG10 overexpression is related to the dismal prognosis and promotes the growth and migration of hepatocellular carcinoma cells via cyclin B1/CDK1 and CDK2.

Although the expression of autophagy-related 10 (ATG10) is known to be associated with the poor prognosis of cancer patients by enhancing cancer cell growth and migration, the roles of ATG10 in hepatocellular carcinoma (HCC) remains to be determined. In this study, the expression of ATG10 in HCC was analyzed using the data from TCGA databases and was further verified in the clinical samples from our patients. In addition, the relationships of ATG10 expression with clinical features, diagnosis and prognosis, as well as the predictive values of ATG10 expression in overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) were explored. Furthermore, the expression and the prognostic values of ATG10 co-expressed genes were also identified in HCC, which was used to construct prognostic nomograms. Our data showed that the expression level of ATG10 was significantly increased in HCC, and the elevated ATG10 expression was associated with poor prognosis. Moreover, cells with ATG10 knockdown were used to investigate the effects of ATG10 on HCC cell proliferation and migration. We found that silencing ATG10 inhibited the proliferation, migration, and invasion of HCC cells, which was related to the protein expression of cyclin B1, CDK1, and CDK2. Similarly, the overexpression of ATG10 co-expressed genes ATG12, LARS1, CWC27, and SLC30A5 in HCC patients were also associated with the OS, DSS, and PFI. The risk models and nomograms based on ATG10 and ATG10 co-expressed genes indicated the correclation between their expression and the dismal prognosis in HCC patients. In conclusion, ATG10 expression was elevated in HCC and was associated with poor prognosis. Inhibition of ATG10 expression could attenuate cancer progression. ATG10-related nomograms and risk models could be used clinically to evaluate the prognosis of HCC patients.