Radiation-primed TGF-ß trapping by engineered extracellular vesicles for targeted glioblastoma therapy.

The poor outcome of glioblastoma multiforme (GBM) treated with immunotherapy is attributed to the profound immunosuppressive tumor microenvironment (TME) and the lack of effective delivery across the blood-brain barrier. Radiation therapy (RT) induces an immunogenic antitumor response that is counteracted by evasive mechanisms, among which transforming growth factor-ß (TGF-ß) activation is the most prominent factor. We report an extracellular vesicle (EV)-based nanotherapeutic that traps TGF-ß by expressing the extracellular domain of the TGF-ß type II receptor and targets GBM by decorating the EV surface with RGD peptide. We show that short-burst radiation dramatically enhanced the targeting efficiency of RGD peptide-conjugated EVs to GBM, while the displayed TGF-ß trap reversed radiation-stimulated TGF-ß activation in the TME, offering a synergistic effect in the murine GBM model. The combined therapy significantly increased CD8+ cytotoxic T cells infiltration and M1/M2 macrophage ratio, resulting in the regression of tumor growth and prolongation of overall survival. These results provide an EV-based therapeutic strategy for immune remodeling of the GBM TME and eradication of therapy-resistant tumors, further supporting its clinical translation.

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MiRNAs are a class of small non-coding RNAs, which regulate gene expression post-transcriptionally by partial complementary base pairing. Aberrant miRNA expressions have been reported in tumor tissues and peripheral blood of cancer patients. In recent years, artificial intelligence algorithms such as machine learning and deep learning have been widely used in bioinformatic research. Compared to traditional bioinformatic tools, miRNA target prediction tools based on artificial intelligence algorithms have higher accuracy, and can successfully predict subcellular localization and redistribution of miRNAs to deepen our understanding. Additionally, the construction of clinical models based on artificial intelligence algorithms could significantly improve the mining efficiency of miRNA used as biomarkers. In this article, we summarize recent development of bioinformatic miRNA tools based on artificial intelligence algorithms, focusing on the potential of machine learning and deep learning in cancer-related miRNA research.

Deciphering Microbiome, Transcriptome, and Metabolic Interactions in the Presence of Probiotic Lactobacillus acidophilus against Salmonella Typhimurium in a Murine Model.

Salmonella enterica serovar Typhimurium (S. Typhimurium), a foodborne pathogen that poses significant public health risks to humans and animals, presents a formidable challenge due to its antibiotic resistance. This study explores the potential of Lactobacillus acidophilus (L. acidophilus 1.3251) probiotics as an alternative strategy to combat antibiotic resistance associated with S. Typhimurium infection. In this investigation, twenty-four BALB/c mice were assigned to four groups: a non-infected, non-treated group (CNG); an infected, non-treated group (CPG); a group fed with L. acidophilus but not infected (LAG); and a group fed with L. acidophilus and challenged with Salmonella (LAST). The results revealed a reduction in Salmonella levels in the feces of mice, along with restored weight and improved overall health in the LAST compared to the CPG. The feeding of L. acidophilus was found to downregulate pro-inflammatory cytokine mRNA induced by Salmonella while upregulating anti-inflammatory cytokines. Additionally, it influenced the expression of mRNA transcript, encoding tight junction protein, oxidative stress-induced enzymes, and apoptosis-related mRNA expression. Furthermore, the LEfSe analysis demonstrated a significant shift in the abundance of critical commensal genera in the LAST, essential for maintaining gut homeostasis, metabolic reactions, anti-inflammatory responses, and butyrate production. Transcriptomic analysis revealed 2173 upregulated and 506 downregulated differentially expressed genes (DEGs) in the LAST vs. the CPG. Functional analysis of these DEGs highlighted their involvement in immunity, metabolism, and cellular development. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis indicated their role in tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), chemokine, Forkhead box O (FOXO), and transforming growth factor (TGF-ß) signaling pathway. Moreover, the fecal metabolomic analysis identified 929 differential metabolites, with enrichment observed in valine, leucine, isoleucine, taurine, glycine, and other metabolites. These findings suggest that supplementation with L. acidophilus promotes the growth of beneficial commensal genera while mitigating Salmonella-induced intestinal disruption by modulating immunity, gut homeostasis, gut barrier integrity, and metabolism.

A Critical Review of the Effectiveness of Biochar Coupled with Arbuscular Mycorrhizal Fungi in Soil Cadmium Immobilization.

Cadmium-contaminated soil significantly threatens global food security and human health. This scenario gives rise to significant worries regarding widespread environmental pollution. Biochar and arbuscular mycorrhizal fungi (AMF) can effectively immobilize cadmium in the soil in an environmentally friendly way. Existing studies have separately focused on the feasibility of each in remediating polluted soil. However, their association during the remediation of cadmium-polluted soils remains unclear. This review paper aims to elucidate the potential of biochar, in conjunction with AMF, as a strategy to remediate soil contaminated with cadmium. This paper comprehensively analyzes the current understanding of the processes in cadmium immobilization in the soil environment by examining the synergistic interactions between biochar and AMF. Key factors influencing the efficacy of this approach, such as biochar properties, AMF species, and soil conditions, are discussed. The influences of biochar-AMF interactions on plant growth, nutrient uptake, and overall ecosystem health in cadmium-contaminated environments are highlighted. This review indicates that combining biochar and AMF can improve cadmium immobilization. The presence of AMF in the soil can create numerous binding sites on biochar for cadmium ions, effectively immobilizing them in the soil. Insights from this review contribute to a deeper understanding of sustainable and eco-friendly approaches to remediate cadmium-contaminated soils, offering potential applications in agriculture and environmental management.

Two undescribed compounds from Aspergillus Niger, an endophytic fungus isolated from Camellia flavida.

A new naphtho-γ-pyrone dimer, asperosperma A, and a new methyl nicotinate derivative, asperosperma B, with 12 known compounds were isolated from the endophytic fungus Aspergillus niger from the stem of Camellia flavida. Their structure was elucidated by NMR, ECD spectrum, and HR-ESI-MS data. Asperosperma A exhibited a highly cytotoxicity against H460 and 4T1 cancer cells with the IC50 values were 0.37 ± 0.06 and 2.04 ± 0.79 µM, respectively. Moreover, it showed a highly sensitive against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant S. aureus.

Variations in serum low-density lipoprotein and sST2 among heart failure patients with different ejection fraction groups and their clinical significance.

OBJECTIVE: This study aimed to examine the changes in serum Low Density Lipoprotein Cholesterol (LDL-C) and Soluble Growth Stimulating Expressed Gene 2 Protein (sST2) among Heart Failure (HF) patients with varying ejection fractions and their clinical significance, providing a reference for the clinical assessment of HF severity. METHODS: A total of 238 HF patients treated in our hospital's cardiology department from September 2019 to December 2021 were selected; 68 patients hospitalized in the same period were selected as the control group. General information, LDL-C and echocardiographic results of admitted patients were collected. According to LVEF results and the latest European Society of Cardiology standards in 2021, HF patients were categorized into those with HFpEF (n = 95), HFmrEF (n = 60), and HFrEF (n = 83). Meanwhile, venous blood was collected to determine sST2 and NT-proBNP to compare and analyze the changes and clinical significance of sST2 and LDL-C across the groups. RESULTS: Compared to the control group, the HF group showed significant differences in age, gender, heart rate, smoking history, history of atrial fibrillation, history of diabetes, LVEDD, LVEF, sST2, and NT-proBNP levels (P < .05), but not in LDL-C levels. Significant differences (P < .05) were also found among the 3 HF groups in terms of age, gender, history of atrial fibrillation, LVEDD, LVEF, LDL-C, sST2, and NT-proBNP levels, with an increase in LVEDD, LDL-C, sST2, and NT-proBNP values as the ejection fraction decreased. ROC curve analysis indicated that the area under the curve (AUC) for sST2 in diagnosing HF was 0.915 (P < .05), with an optimal cutoff value of 23.71 ng/mL, a sensitivity of 76.5%, and a specificity of 95.6%; LDL-C was not a significant diagnostic marker for HF (P > .05). Coronary artery disease, NT-proBNP, and sST2 were identified as risk factors for HF. With each unit increase in coronary artery disease, the risk of HF increased by 36.3%; for NT-proBNP, the risk increased by 1.3% per unit; and for sST2, it increased by 18.3% per unit. CONCLUSION: As the ejection fraction decreases in HF patients, serum sST2 and LDL-C values progressively increase, which is clinically significant for predicting the severity of HF. sST2 is an independent risk factor for HF and can enhance the diagnostic accuracy for HF.

A Versatile Platform to Generate Prodrugs with Rapid and Precise Albumin Hitchhiking and High Cargo Loading for Tumor-Targeted Chemotherapy.

Due to its tumor homing and long serum half-life, albumin is an ideal drug carrier for chemotherapy. For endogenous albumin hitchhiking with high cargo loading, a trimeric albumin-binding domain (ABD), i.e., ABD-Tri is designed by fusing an ABD with high specificity and affinity for albumin to a self-trimerizing domain (Tri) with an additional cysteine residue. ABD-Tri is highly (40 mg L-1) expressed as soluble and trimeric proteins in Escherichia coli (E. coli). Once mixed together, ABD-Tri rapidly and specifically forms a stable complex with albumin under physiological conditions without obviously changing its receptor- and cell-binding and tumor-homing properties. Maleimide-modified prodrugs are highly effectively conjugated to ABD-Tri to produce homogenous ABD-Tri-prodrugs with triple cargo loading under physiological conditions by thiol-maleimide click chemistry. Unlike the maleimide moiety, which can only mediate time- and concentration-dependent albumin binding, ABD-Tri mediated fast (within several minutes) albumin binding of drugs even at extremely low concentrations (µg mL-1). Compared to maleimide-modified prodrugs, ABD-Tri-prodrugs exhibit better tumor homing and greater in vivo antitumor effect, indicating that conjugation of chemical drug to ABD-Tri outperforms maleimide modification for endogenous albumin hitchhiking. The results demonstrate that ABD-Tri may serve as a novel platform to produce albumin-binding prodrugs with high cargo-loading capacity for tumor-targeted chemotherapy.

A more accurate relationship between serum androgen and metabolism among healthy, nonobese, reproductive-age women based on liquid chromatography-tandem mass spectrometry.

This study explored a more precise association between androgens and glycolipid metabolism in healthy women of different ages. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio were used as body fat indicators. High-density lipoprotein (HDL), low-density lipoprotein, triglycerides, and total cholesterol were used as lipid markers. Fasting blood glucose (FBG), fasting insulin, and the homeostatic model assessment of insulin resistance were used to assess insulin resistance and glucose metabolism. Liquid chromatography-tandem mass spectrometry was used to measure androgen indicators, including testosterone, sex hormone-binding globulin (SHBG), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). DHEAS levels varied across age groups. Correlation analyses with Spearman's coefficient showed that the free androgen index correlated positively with WC (p = 0.040), FT correlated positively with BMI (p = 0.033) and WC (p = 0.049), SHBG correlated positively with HDL (p = 0.013), and A4 correlated positively with FBG (p = 0.017). Multiple linear regression analysis showed that among healthful women aged 36-40 years, A4 increased with FBG, and SHBG increased with HDL. Even within healthy, nonobese women, lipid and glucose metabolism were robustly correlated with androgens. Yearly metabolic assessments are necessary, particularly for FBG and HDL, since these markers can predict the likelihood of hyperandrogenemia, enabling timely interventions.

Association Between Systemic Immune Inflammation Level and Poor Prognosis Across Different Glucose Metabolism Status in Coronary Artery Disease Patients.

Background: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear. Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes. Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56-1.83]), cardiovascular mortality (2.29 [2.02-2.59]), and cancer mortality (1.29 [1.01-1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality. Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.

Noninvasive radiomics model reveals macrophage infiltration in glioma.

Preoperative MRI is an essential diagnostic and therapeutic reference for gliomas. This study aims to evaluate the prognostic aspect of a radiomics biomarker for glioma and further investigate its relationship with tumor microenvironment and macrophage infiltration. We covered preoperative MRI of 664 glioma patients from three independent datasets: Jiangsu Province Hospital (JSPH, n = 338), The Cancer Genome Atlas dataset (TCGA, n = 252), and Repository of Molecular Brain Neoplasia Data (REMBRANDT, n = 74). Incorporating a multistep post-processing workflow, 20 radiomics features (Rads) were selected and a radiomics survival biomarker (RadSurv) was developed, proving highly efficient in risk stratification of gliomas (cut-off = 1.06), as well as lower-grade gliomas (cut-off = 0.64) and glioblastomas (cut-off = 1.80) through three fixed cut-off values. Through immune infiltration analysis, we found a positive correlation between RadSurv and macrophage infiltration (RMΦ = 0.297, p < 0.001; RM2Φ = 0.241, p < 0.001), further confirmed by immunohistochemical-staining (glioblastomas, n = 32) and single-cell sequencing (multifocal glioblastomas, n = 2). In conclusion, RadSurv acts as a strong prognostic biomarker for gliomas, exhibiting a non-negligible positive correlation with macrophage infiltration, especially with M2 macrophage, which strongly suggests the promise of radiomics-based models as a preoperative alternative to conventional genomics for predicting tumor macrophage infiltration and provides clinical guidance for immunotherapy.

Snoopligase-catalyzed molecular glue enables efficient generation of hyperoligomerized TRAIL variant with enhanced antitumor effect.

Clinical application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is predominantly limited by its inefficient apoptosis induction in tumor cells, which might be improved by using molecular superglue-mediated hyperoligomerization to increase its valency. Here, the minimal superglue peptide pairs, including Snoopligase-catalyzed SnoopTagJr/SnoopDogTag and SpyStapler-catalyzed SpyTag/SpyBDTag, were individually fused at the N- or C-terminus of the TRAIL promoter to produce superglue-fusion TRAIL variants. Similar to native trivalent TRAIL, these superglue-fusion TRAIL variants were highly expressed in Escherichia coli (E. coli) and spontaneously trimerized. In the presence of Snoopligase or SpyStapler, the trivalent superglue-fusion TRAIL variants were predominantly crosslinked into hexavalent TRAIL variants. Nevertheless, Snoopligase was more efficient than SpyStapler in the production of hexavalent TRAIL variants. In particular, Snoopligase-catalyzed trivalent TRAIL variants with N-terminal fusion of SnoopTagJr/SnoopDogTag produced hexavalent SnHexaTR with the highest yield (∼70%). The in vitro cytotoxicity of SnHexaTR was 10-40 times greater than that of TRAIL in several tumor cells. In addition, compared to trivalent TRAIL, hexavalent SnHexaTR showed a longer serum half-life and greater tumor uptake, which resulted in eradication of 50% of tumor xenografts of TRAIL-sensitive COLO 205. In mice bearing TRAIL-resistant HT-29 tumor xenografts, hexavalent SnHexaTR combined with bortezomib encapsulated in liposomes also showed robust tumor growth suppression, indicating that hyperoligomerization mediated by minimal molecular superglue significantly increased the cytotoxicity and antitumor effect of TRAIL. As a novel anticancer agent candidate, the hexavalent SnHexaTR has great potential for clinical application in cancer therapy.

Establishment and assessment of a preclinical model of acute kidney injury induced by contrast media combined acute myocardial ischemia reperfusion surgery.

Acute kidney injury (AKI) is a common complication after acute myocardial infarction (AMI) in clinical practice, and the majority of previous preclinical models were induced by a single factor. The objective of the present study was to establish a stable preclinic model of AKI induced by contrast media (CM) with acute myocardial ischemia reperfusion surgery and to identify the effect of oxidative stress on kidney injury. Rats were treated individually or with CM or myocardial ischemia reperfusion surgery. Renal baseline and AKI parameters, the level of oxidative stress and histopathological images were examined along with AKI biomarkers. Results showed the incidence of AKI in the CM group and ischemia reperfusion injury (IRI) group was 40%, χ2 test (P<0.05 vs. CM-IRI) and 35%, χ2 test (P<0.05 vs. CM-IRI) and the combination group had the highest incidence rate 75%. IRI surgery combined with CM diminished kidney function and induced oxidative stress by increasing creatinine, blood urea nitrogen and reactive oxygen species levels. Western blotting showed that the early AKI biomarker of NGAL and KIM-1 increased and that the combination group had the highest value. Pathology damage exhibited severe kidney damage in the combination group compared with other control groups. The present research established a reliable preclinic model of post-AMI AKI with a stable and high postoperative AKI rate. Additionally, CM was demonstrated to exacerbate AKI caused by acute myocardial infarction through oxidative stress and, thus, oxidative stress may be a potential therapeutic target.

S1PR2 is Important for Cigarette Smoke-induced Pyroptosis in Human Bronchial Epithelial Cells.

BACKGROUND: Chronic obstructive pulmonary disease and other respiratory inflammatory diseases are often associated with cigarette smoke exposure. However, the underlying molecular mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the role of sphingosine-1-phosphate receptor 2 (S1PR2) in cigarette smoke extract (CSE)-induced inflammation and pyroptosis in human bronchial epithelial (HBE) cells. METHODS: CSE was administered to HBE cells and inflammation and pyroptosis were assessed. The mRNA levels of S1PR2, NLRP3, IL-1ß, and IL-18 in HBE cells were detected by quantitative RT-PCR. Secreted protein levels of IL-1ß and IL-18 in the culture supernatants were detected using enzyme-linked immunosorbent assay. Western blotting was used to measure the levels of S1PR2 and pyroptosis-related proteins (NLRP3, ASC, caspase-1, GSDMD, IL-1ß, and IL-18). RESULTS: Our study revealed an upregulated expression of S1PR2, NLRP3, ASC, caspase-1, GSDMD, IL-1ß, and regulated IL-18 in HBE cells after CSE exposure. Genetic blockage of S1PR2 could reverse the increased expression of these proteins related to CSE-induced pyroptosis. Conversely, S1PR2 overexpression increased CSE-induced pyroptosis by upregulating the expression of NLRP3, ASC, caspase-1, GSDMD, IL-1ß, and IL-18 in HBE cells. CONCLUSIONS: Our results revealed that a novel S1PR2 signaling pathway may be involved in the pathogenesis of CSE-induced inflammation and pyroptosis in HBE cells. Thus, S1PR2 inhibitors could be an effective treatment for cigarette smoke-induced airway inflammation and injury.

Elevation of hemoglobin A1c increases the risk of decline in left ventricular systolic function among patients with coronary artery disease.

AIMS: The aim of this study was to investigate the association of HbA1c and left ventricular (LV) systolic function among patients with coronary artery disease (CAD). METHODS: CAD patients from the Cardiorenal ImprovemeNt II (CIN-II, NCT05050877) registry were included in the study. They were separated into four groups based on HbA1c levels (Q1: HbA1c<5.7%; Q2: 5.7% ≤ HbA1c < 6.1%; Q3: 6.1% ≤ HbA1c < 6.9%; Q4: HbA1c ≥ 6.9%). The endpoint was decline in LV systolic function, defined as an absolute decrease in LV ejection fraction (LVEF) ≥10% from baseline to follow-up with 3-12 months. The association of HbA1c and LVEF was assessed by logistics regression models. RESULTS: CAD patients (n = 3,994) (age 62.9 ± 10.6 years; 22.2% female) were included in the final analysis. A decline in LV systolic function was recorded in 429 (11%) patients during follow-up. After fully adjusting for confounders, HbA1c was significantly associated with the high risk of decline in LV systolic function (OR 1.12 [95%CI 1.05-1.20] P = 0.001). By stratifying HbA1c as four groups, there is a significantly increased risk of decline in LV systolic function when HbA1c ≥6.1% (Q2, Q3 and Q4 vs Q1, with OR 1.22 [0.88-1.68] P = 0.235; OR 1.48 [1.07-2.05] P = 0.019; OR 1.60 [1.160-2.22] P = 0.004, respectively). Meanwhile, patients with decline in LV systolic function had a higher risk of cardiovascular death. CONCLUSIONS: Elevated HbA1c is a predictor of decline in LV systolic function in CAD patients. Clinicians should be aware of the risk of decline in LV systolic function in CAD patients with elevated HbA1c, and take measures as soon as possible.

Elevated systemic immune inflammation level increases the risk of total and cause-specific mortality among patients with chronic kidney disease: a large multi-center longitudinal study.

BACKGROUND: Chronic kidney disease (CKD) is inherently a complex immune-inflammatory condition, and heightened inflammation and immune dysfunction are closely related to an increased risk of death. However, evidence regarding the relationship between immune-inflammatory levels and all-cause, cardiovascular, and cancer mortality among patients with CKD is scarce. METHODS: Patients with non-dialysis dependent CKD undergoing coronary angiography (CAG) were included from five Chinese tertiary hospitals. Systemic immune inflammation index (SII) was calculated by multiplying peripheral platelet count with neutrophil-to-lymphocyte ratio, and patients were categorized into four groups by SII quartiles. Cox regression models and competing risk Fine and Gray models were used to examining the relationships between SII levels and all-cause, cardiovascular, and cancer mortality. RESULTS: A total of the 19,327 patients (68.8 ± 10.03 years, female 32.0%) were included in this study. During a median follow-up of 4.5 years, 5,174 deaths occurred, including 2,861 cardiovascular deaths and 375 cancer deaths. Controlling for confounders, all-cause mortality (Q2, Q3, Q4: hazard ratio(HR) [95 CI%] = 1.15 [1.06-1.26], 1.30 [1.19-1.42], 1.48 [1.35-1.62], respectively; p for trend < 0.001) and cardiovascular mortality (Q2, Q3, Q4: HR [95 CI%] = 1.16 [1.03-1.31], 1.40 [1.24-1.58], 1.64 [1.44-1.85], respectively; p for trend < 0.001) increased with higher SII levels, and SII levels was related to cancer mortality comparing last quartile to first quartile of SII (Q2, Q3, Q4: HR [95 CI%] = 1.12 [0.83-1.52], 1.22 [0.90-1.67], 1.50 [1.09-2.08], respectively; p for trend < 0.001). CONCLUSION: Elevated immune inflammation level on admission was an independent risk factor for all-cause, cardiovascular, and cancer mortality among CKD patients. Further research is needed to validate the predictive value of SII for mortality risk among CKD patients.

Association between Vitamin D Status and Mortality among Adults with Diabetic Kidney Disease.

Objective: Emerging evidence demonstrates that vitamin D status contributes to the incidence of diabetic kidney disease (DKD). However, the causal relationships between vitamin D and mortality among individuals with DKD are inconclusive. Our study is aimed at exploring the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality among adults with DKD. Research Design and Methods. Our study included 1,202 adult participants with DKD from the National Health and Nutrition Examination Survey (NHANES) 2001-2014. Cox and competing-risks regression were used to estimate hazard ratios (HRs) and 95% CIs for associations between 25(OH)D concentrations and survival. Results: The overall mean serum 25(OH)D concentration was 55.9 ± 26.3. Vitamin D deficiency (25(OH)D < 50 nmol/l), insufficiency group (50 ≤ 25(OH)D < 75 nmol/l), and sufficiency group (25(OH)D ≥ 75 nmol/l) were observed in 552 (45.9%), 409 (34.0%), and 241 (20.0%) participants, respectively. Higher levels of vitamin D were significantly associated with improved all-cause and nonaccident- and malignant neoplasm-cause mortality among individuals with DKD after adjusting for the potential confounding factors. Conclusions: We observed widespread vitamin D deficiency or insufficiency in DKD patients. Higher 25(OH)D values were significantly correlated with lower risk of mortality after adjusting for confounding variables.

Circ_ZFR affects FABP7 expression to regulate breast cancer progression by acting as a sponge for miR-223-3p.

BACKGROUND: Breast cancer (BC) is a common malignancy in women. Circular RNAs (circRNAs) have been reported to play a key role in the development of BC; however, the effect of circular RNA zinc finger RNA binding protein (circ_ZFR) in BC is unknown. METHODS: Abundances of circ_ZFR, fatty acid binding protein 7 (FABP7), and microRNA-223-3p (miR-223-3p) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure of circ_ZFR was validated by RNase R treatment. Cell proliferation, migration, invasion, and apoptosis were assessed by colony formation, cell counting kit-8, Transwell, flow cytometry assays, respectively. All protein levels were determined by Western blot. Dual-luciferase reporter assay was used to confirm the relationship between miR-223-3p and circ_ZFR or FABP7. A xenograft model was established to understand the effect of circ_ZFR on BC cell growth in vivo. RESULTS: The expression levels of circ_ZFR and FABP7 were higher in BC tissues and cell lines, whereas miR-223-3p expression was lower. Knockdown of circ_ZFR or FABP7 in BC cells reduced proliferation, migration, invasion, and epithelial mesenchymal transition (EMT), and induced apoptosis in vitro, whereas the opposite effects were observed in circ_ZFR-overexpressed cells. Furthermore, circ_ZFR might act as a sponge for miR-223-3p to regulate FABP7 expression, thereby promoting the progression of BC cells in vitro and in vivo. CONCLUSION: Circ_ZFR might act as a miRNA sponge for miR-223-3p to regulate FABP7, thereby promoting proliferation, migration, invasion, and EMT of BC cells, and inhibiting cell apoptosis.

The Efficacy of Resin Hemoperfusion Cartridge on Inflammatory Responses during Adult Cardiopulmonary Bypass.

AIM: This study aimed to evaluate the efficacy of the resin hemoperfusion device (HA380 hemoperfusion cartridge) on inflammatory responses during adult cardiopulmonary bypass (CPB). METHODS: Sixty patients undergoing surgical valve replacement were randomized into the HP group (n = 30) with an HA380 hemoperfusion cartridge in the CPB circuit or the control group (n = 30) with the conventional CPB circuit. The results of routine blood tests, blood biochemical indexes, and inflammatory factors were analyzed at V0 (pre-CPB), V1 (CPB 30 min), V2 (ICU 0 h), V3 (ICU 6 h), and V4 (ICU 24 h). RESULTS: The HP group had significantly lower levels of IL-6, IL-8, and IL-10. Significant estimation of group differences in the generalized estimating equation (GEE) models was also observed in IL-6 and IL-10. The HP group had significantly lower levels of creatinine (Cr), aminotransferase (AST), and total bilirubin (TBil) compared to the control group. The estimation of differences of Cr, AST, and TBil all reached statistical significance in GEE results. The HP group had significantly less vasopressor requirement and shorter mechanical ventilation time and ICU stay time as compared to the control group. CONCLUSION: The HA380 hemoperfusion cartridge could effectively reduce the systemic inflammatory responses and improve postoperative recovery of patients during adult CPB.

Study on the Inhibitory Effect of Curcumin on GBM and Its Potential Mechanism.

BACKGROUND: Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system (CNS). However, current GBM treatments are ineffective, signifying the great importance of exploring new therapeutic targets. Curcumin has been found to be a natural compound with an anticancer potential. However, its targets and mechanisms in GBM are still unclear. METHODS: Differentially expressed genes (DEGs) were screened from the GBM dataset in the GEO database and intersected with the target genes of curcumin to select potential target genes. Subsequently, survival analysis was performed with the GEPIA database to confirm the effect of target genes on the prognosis of GBM, and functional enrichment analysis was performed using the DAVID database. In vitro, CCK-8 assay was used to screen the appropriate concentration of curcumin; scratch and transwell invasion assays were used to evaluate the effect of curcumin on the migration and invasion abilities of GBM cells. Furthermore, RT-qPCR and Western blotting were used to detect changes in target genes and flow cytometry was used to assess the apoptosis level. RESULTS: A total of 16 target genes of curcumin and GBM were obtained, among which ENO1, MMP2, and PRKD2 significantly affected the prognosis (P < 0.05). We further selected ENO1 for functional enrichment analysis and found that it was enriched in the glycolytic pathway. Meanwhile, in vitro experiments showed that curcumin could inhibit the migration and invasion of U251 cells and promote apoptosis (P < 0.05). CONCLUSION: ENO1 could be a possible target for curcumin in the suppression of GBM cells.