Zinc hexacyanoferrate/g-C3N4 nanocomposites with enhanced photothermal and photodynamic properties for rapid sterilization and wound healing.

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.

Circulating GDF-15 in relation to the progression and prognosis of chronic kidney disease: A systematic review and dose-response meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) typically exhibit circulating growth differentiation factor-15 (GDF-15) at high levels. This meta-analysis aimed to evaluate the potential value of GDF-15 in predicting CKD progression and prognosis. Furthermore, when sufficient information was provided, the dose-response correlation was studied. METHODS: Studies were searched in Web of Science, Embase, and PubMed from inception until November 2022. By using random- or fixed-effects models, the pooled effect size was estimated in accordance with heterogeneity in existing research. RESULTS: This study covered 14 studies from 12 articles with 7813 subjects participating in the research. CKD patients in the top GDF-15 tertile had notably higher risks of CKD progression (HR 2.60, 95% CI 2.06-3.27), all-cause mortality (HR 2.05, 95% CI 1.44-2.92), cardiovascular mortality (HR 2.82, 95% CI 1.85-4.30), and cardiovascular events (HR 2.74, 95% CI 2.21-3.40), as compared to CKD patients in the bottom tertile. In the dose-response study, the risks for CKD progression, all-cause death, cardiovascular death, and cardiovascular events were increased by 31% (HR 1.31, 95% CI 1.06-1.61), 44% (HR 1.44, 95% CI 1.08-1.92), 67% (HR 1.67, 95% CI 1.37-2.03), and 55% (HR 1.55, 95% CI 1.31-1.83), respectively, with per 1 ng/mL increase in GDF-15. The positive linear correlations between GDF-15 and CKD progression and prognosis in a certain GDF-15 concentration range of approximately 0-3 ng/mL were indicated by the dose-response curve. CONCLUSIONS: Circulating GDF-15 independently predicted CKD progression and worse prognosis; however, the predicted correlations may fall into a specific range of GDF-15 concentrations.

Low Testosterone Level and Risk of Adverse Clinical Events among Male Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Cohort Studies.

The phenomenon of low testosterone level is extremely common in male patients with chronic kidney diseases (CKDs). This meta-analysis aimed to evaluate whether the low circulating testosterone could independently predict adverse outcomes among male patients with chronic kidney diseases (CKDs). The data till May 2022 were systematically searched from Pubmed, Web of Science, and Embase from inception. Studies meeting the PICOS (population, intervention/exposure, control/comparison, outcomes, and study design) principles were included in this meta-analysis. Study-specific effect estimates were pooled using fixed-effects (I 2 > 50%) or random-effects models (I 2 < 50%). Ultimately, 9 cohort studies covering 5331 patients with CKDs were involved in this meta-analysis. The results suggested that per 1-standard deviation (SD) decrease in total testosterone independently increased the risk of all-cause mortality by 27% [hazard risk (HR) 1.27, 95% confidence interval (CI) 1.16-1.38], cardiovascular mortality by 100% (HR 2.00, 95% CI 1.39-2.86), cardiovascular events by 20% (HR 1.20, 95% CI 1.04-1.39), and infectious events by 41% (HR 1.41, 95% CI 1.08-1.84). Besides, with per 1-SD decrease in free testosterone, the risk of overall adverse events increased by 66% (HR 1.66, 95% CI 1.34-2.05). Stratified analyses indicated that the negative relationship of the total testosterone with all-cause death risk was independent of factors involving age, race, body mass index, diabetes, hypertension, C-reactive protein, creatinine, and sex hormone binding globulin. In conclusion, it was identified that low endogenous testosterone could serve as an independent predictor of adverse clinical events among male patients with CKDs.

Circulating Trimethylamine-N-Oxide and Risk of All-Cause and Cardiovascular Mortality in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Background: Trimethylamine-N-oxide (TMAO) is expected to be a prognostic biomarker among patients suffering from chronic kidney disease (CKD). However, investigations on the association between TMAO and CKD prognosis are conflicting. In the present article, we aimed to assess the relationship of circulating TMAO with the risk of all-cause and cardiovascular mortality among CKD patients by a meta-analysis. Methods: Data were collected from PubMed, EMBASE, and Web of Science for systematically searching related literature (last update: February 2022). The multivariable-adjusted hazard risks (HR) and their 95% confidence intervals (CI) were pooled using random effects models. Results: Eleven prospective cohort studies covering 7,899 CKD patients were enrolled in this meta-analysis. When comparing individuals in the top and bottom baseline TMAO levels thirds, the multivariate adjusted pooled HR was 1.29 (95% CI 1.11-1.51, P = 0.001) for all-cause mortality, and 1.45 (95% CI 1.01-2.09, P = 0.043) for cardiovascular death. For continuous variables, per 1 unit increase of circulating TMAO levels was associated with a 3% higher all-cause mortality (HR 1.03, 95% CI 1.00-1.06, P = 0.032), but not significantly associated with cardiovascular death (HR 1.08, 95% CI 0.92-1.27, P = 0.346). Stratified analyses revealed that the positive relationship between TMAO and all-cause mortality remained significant after adjusting for diabetes, blood pressure, blood lipid, renal function, or inflammatory parameters. Conclusion: Higher circulating TMAO was associated with an increased mortality risk among patients with CKD, and this relationship may be dependent on TMAO dose and independent of renal function, inflammation, diabetes, hypertension, and dyslipidemia. Systematic Review Registration: [https://www.INPLASY.COM], identifier [INPLASY2021100049].

Fetuin-A to adiponectin ratio is an independent indicator of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes mellitus.

AIMS: The purpose of this research was to explore the associations of fetuin-A, adiponectin, and fetuin-A/adiponectin ratio (F/A ratio) with subclinical atherosclerosis as evaluated by carotid intima-media thickness (CIMT) in cases with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A total of 283 newly diagnosed T2DM patients were enrolled in this study. Serum fetuin-A and adiponectin levels were determined with an ELISA method. Other clinical and biochemical parameters were also collected. RESULTS: Significant linear increases in waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure, homoeostasis model assessment of insulin resistance, C-reactive protein (CRP) and F/A ratio, and a significant linear decrease in adiponectin with increasing tertiles of CIMT were observed (P for trends <0.05). However, no significant correlation between fetuin-A and CIMT was detected (P > 0.05). In multivariate logistic regression models, WHR, SBP and F/A ratio were independently correlated with higher CIMT. Receiver operating characteristic curve analysis indicated that F/A ratio had a better predictive power for higher CIMT than adiponectin and fetuin-A, with an area under the curve of 0.802, 0.713 and 0.646, respectively. CONCLUSION: F/A ratio is an independent indicator of subclinical atherosclerosis in patients with newly diagnosed T2DM.

Fabrication of cerium doped carbon dots with highly radical scavenging activity alleviates ferroptosis-induced oxidative damage.

Ferroptosis as an iron-dependent lipid peroxidation process causes sevely oxidative damage of cell, but lack of highly efficient and recycable antioxidant agents. To this end, cerium doped carbon dots (Ce-doped CDs) with radical scavenging activity were synthesized using a simple microwave-assisted hydrothermal carbonization. The resultant Ce-doped CDs exhibited an ultra-small size of only approximately 2.6 nm, excellent dispersion in water as well as optical performance. Taking advantage of inherent ultra-small size, Ce-doped CDs were endowed with high Ce3+/Ce4+ratio, which significantly enhanced their radical scavenging activity. Meanwhile, the Ce-doped CDs with superior biocompatibility could enter cells quickly and then localized in the cytoplasm. As we expected, the Ce-doped CDs strongly protected cells from oxidative damage of erastin-mediated ferroptosis. These findings suggest that the as-prepared Ce-doped CDs have the potential to be antioxidant drugs against for ferroptosis-induced oxidative damage.

Fetuin-a to adiponectin ratio is a sensitive indicator for evaluating metabolic syndrome in the elderly.

BACKGROUND: Fetuin-A and adiponectin present significant associations, supported by recent evidence, with metabolic syndrome (MS) featuring hyperglycemia, central obesity and insulin resistance as the main components, but their biological functions are opposite. The aim of this study was to verify whether fetuin-A/adiponectin ratio (F/A ratio) is a more sensitive indicator for evaluation of MS than either fetuin-A or adiponectin. METHODS: In this cross-sectional study, 465 elderly subjects were selected from the physical examination database. Serum levels of fetuin-A and adiponectin were measured using an enzyme-linked immunosorbent assay (ELISA) method. Spearman's rank correlation coefficient, linear regression and logistic regression analysis were adopted to estimate the correlations of fetuin-A, adiponectin and F/A ratio with MS and its components, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive values of the aforesaid indices. RESULTS: Compared with fetuin-A or adiponectin, F/A ratio was significantly associated with all the components of MS, and this correlation was significant even after adjusting potential confounding factors (P < 0.05). Logistic regression analysis indicated that F/A ratio presented a stronger correlation with incident MS (adjusted OR: 1.466; 95% CI: 1.189-1.808) than fetuin-A (adjusted OR: 1.100; 95% CI: 1.020-1.186) and adiponectin (adjusted OR: 0.760; 95% CI: 0.664-0.871) alone. ROC analysis revealed that F/A ratio achieved a larger area under curve (AUC) than fetuin-A and adiponectin, with their AUC values of 0.755, 0.709 and 0.708, respectively. CONCLUSION: F/A ratio is a more sensitive index for evaluating MS than either fetuin-A or adiponectin in the elderly.

One-pot synthesis of cerium and praseodymium co-doped carbon quantum dots as enhanced antioxidant for hydroxyl radical scavenging.

The antioxidant activity of ceria nanoparticles is tightly regulated by size distribution and heteroatom doping. Inspired by this rule, cerium and praseodymium codoped carbon quantum dots (Ce/Pr-CQDs) were synthesized through the one-pot hydrothermal carbonization method. Taking intrinsic advantage of CQDs, the resultant Ce/Pr-CQDs exhibited uniform and ultra-small morphology with an average size of 2.8 nm, which led to an increased proportion of Ce3+. In addition, the doping of Pr into Ce-CQDs improved the redox properties. As we expected, the Ce/Pr-CQDs possessed enhanced hydroxyl radical scavenging properties compared with the cerium-doped carbon quantum dots (Ce-CQDs). Furthermore, Ce/Pr-CQDs with favorable biocompatibility and negligible cytotoxicity are readily internalized into cytoplasm, decreasing the level of reactive oxygen species (ROS). Taken together, the resultant Ce/Pr-CQDs displayed great potential for applications relating to oxidative-stress-associated disease.

Platelet indices in patients with chronic inflammatory arthritis: a systematic review and meta-analysis.

Correlation between platelet indices and chronic inflammatory arthritis (CIA) remains a moot point today. This meta-analysis aimed to evaluate whether platelet (PLT) count, mean platelet volume (MPV) and platelet distribution width (PDW) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A systematic literature search was performed in PubMed, EMBASE, and Web of Science up to August 2019. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. As a result, 34 studies were included, encompassing 17 on RA, 12 on AS, 3 on PsA and 2 on both RA and AS. In these studies, PLT count was significantly higher in RA (SMD = 0.55, 95% CI = 0.36-0.73, P < .001), AS (SMD = 0.53, 95% CI = 0.36-0.70, P < .001) and PsA patients (SMD = 1.29, 95% CI = 0.82-1.77, P < .001) than that in healthy subjects, while MPV and PDW presented nonsignificant differences in these intergroup comparisons (P > .05), and similar results were observed in subgroup analyses. The meta-regression analysis demonstrated that there were strong positive correlations between erythrocyte sedimentation rate and PLT count, and weak correlation trend between the disease activity score and PLT count in both RA and AS subjects without statistically significant difference. The sensitivity analysis indicated that these results were not unduly influenced by any single study. In conclusion, this meta-analysis demonstrated that PLT count was elevated in CIA patients and could be suitable for evaluating the disease activity, whereas MPV and PDW were independent of CIA.

Circulating Fetuin-A and Risk of All-Cause Mortality in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Background: Investigations on the association of circulating fetuin-A with all-cause mortality risk in patients with chronic kidney disease (CKD) are conflicting. This meta-analysis aimed to provide a comprehensive estimation of the relationship between fetuin-A and all-cause mortality in CKD patients. Methods: A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library up until 12 December 2018. Hazard risk (HR) and 95% confidence interval (CI) were pooled using random-effect or fixed-effect model models. Results: A total of 13 studies comprising 5,169 CKD patients were included in the meta-analysis. In a comparison of individuals in the bottom third vs. the top third of baseline fetuin-A levels, the pooled multivariate-adjusted HR for the risk of all-cause mortality was 1.92 (95% CI 1.31-2.80), and the significant association was observed only in dialysis patients, but not non-dialysis patients. When fetuin-A was treated as continuous variables, per 0.1 g/L increase of fetuin-A levels was associated with a 8% lower mortality risk in dialysis patients (HR 0.92, 95% CI 0.87-0.97, p = 0.001), but per 0.01 g/L was not. Sensitivity analysis indicated the association was not adjusted by diabetes and inflammation. Conclusion: Lower fetuin-A levels are associated with an increased risk of all-cause mortality independent of diabetes and inflammation in dialysis patients, and there may be a dose-response relationship between them.

Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Investigations regarding serum and plasma vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) are conflicting. This meta-analysis is aimed at determining whether serum and plasma VEGF levels are associated with DR and its severity in diabetic patients. METHODS: PubMed and EMBASE were used to search for published studies, and serum and plasma VEGF levels were compared among DR, nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and nondiabetic retinopathy (NDR) patients. Standardized mean differences (SMD) and 95% confidence interval (CI) were pooled using a random effects model. RESULTS: A total of 29 studies comprising 1805 DR (or NPDR or PDR) patients and 1699 NDR patients were included. ELISA was used to evaluate serum or plasma VEGF levels in all except for two studies included in this meta-analysis. Overall, serum VEGF levels were significantly higher in DR patients (SMD: 0.74, 95% CI: 0.44-1.03) than those in NDR patients, while plasma VEGF levels were not in the comparison (SMD: 0.40, 95% CI: -0.13-0.92). Similarly, NPDR (SMD: 0.51, 95% CI: 0.22-0.80) and PDR (SMD: 1.32, 95% CI: 0.79-1.85) patients had higher serum VEGF levels compared with NDR patients, but the difference was not significant in plasma samples (SMD: 0.24, 95% CI: -0.47-0.95; SMD: 0.37, 95% CI: -0.30-1.05). In addition, serum VEGF levels were higher in PDR patients than those in NPDR patients (SMD: 0.87, 95% CI: 0.41-1.33), but plasma VEGF levels were not (SMD: -0.00, 95% CI: -0.31-0.31). The subgroup and metaregression analysis revealed that the study location, study design, and publication year of a study have certain influence on heterogeneity between studies in serum or plasma samples. CONCLUSIONS: VEGF levels in the serum instead of those in the plasma correlate to the presence and severity of DR in diabetic patients. Further large-scale studies are required to confirm these findings.

Hyaluronic Acid-Functionalized Gadolinium Doped Iron Oxide Nanoparticles for Atherosclerosis-Targeted Mr Imaging.

Magnetic resonance imaging (MRI) contrast agents (CTs) with both positive (T1) and negative (T2) contrast abilities have attracted considerable interests due to their complementary diagnostic information for more precise diagnosis. In this study, gadolinium-doped oxide nanoparticles functionalized by hyaluronic acid (HA-GdIO NPs) were synthesized for atherosclerosis-targeting T1-T2 dual-model MR imaging. The results showed that the HA-GdIO NPs exhibited high magnetic susceptibility and good biocompatibility. After being coated with HA, the HA-GdIO NPs specifically accumulated in the atherosclerosis plaques through targeting CD44-overpression macrophages which played a central role in development of atherosclerotic plaques. Furthermore, the HA-GdIO NPs can provide enhanced T1 and T2 dual phase contrast effects in vitro and in vivo, particularly in the vascular regions of mice. This work may provide a promising idea to construct MRI contrast agents with both effective and targeted contrast abilities for biomedical applications.

Circulating chemerin levels and gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Chemerin is a novel adipokine which is associated with metabolic syndrome and type 2 diabetes mellitus. However, recent investigations regarding circulating chemerin levels in gestational diabetes mellitus (GDM) are conflicting. This meta-analysis is to evaluate and determine their associations. METHODS: A systematic literature search was performed in PubMed, EMBASE and Web of Science up to 13 December 2017. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. RESULTS: Eleven studies comprising 742 GDM patients and 840 normal pregnant women were included. Circulating chemerin levels were increased in GDM patients compared with healthy pregnant women (SMD: 1.16; 95% CI: 0.29, 2.04; P = 0.009). Subgroup analyses revealed such difference was especially available in the groups of the second trimester (SMD: 1.47; 95% CI: 0.28, 2.67) and mean age < 30 years (SMD: 2.30; 95% CI: 0.69, 3.91) of GDM patients. There was significant heterogeneity among studies (I2 = 98.0%, P < 0.001); however, heterogeneity disappeared or markedly decreased in the subgroups of European populations (I2 = 0.0%, P = 0.531), age ≥ 30 years (I2 = 28.2%, P = 0.223) and WHO diagnostic criteria (I2 = 0.0%, P = 0.490) when stratifying by study location, trimester of chemerin measurement and the diagnostic criteria of GDM. CONCLUSIONS: The elevated levels of circulating chemerin were associated with GDM, which suggests it might play an important role in the pathogenetic mechanism of GDM.

Mean Platelet Volume and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

AIM: To evaluate the association between mean platelet volume (MPV) and gestational diabetes mellitus (GDM). METHODS: A systematic literature search was performed in PubMed, EMBASE, Web of Science, and The Cochrane Library up to 4 September 2017. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. RESULTS: Nineteen studies comprising 1361 GDM patients and 1911 normal pregnant women were included. MPV was increased in GDM patients when compared with healthy pregnant women (SMD: 0.79; 95% CI: 0.43-1.16; P < 0.001). Subgroup analyses revealed that such trend was consistent in the third-trimester (SMD: 1.35; 95% CI: 0.72-1.98), Turkish (SMD: 0.81; 95% CI: 0.43-1.19), and Italian (SMD: 2.78; 95% CI: 2.22-3.34) patients with GDM and the patients diagnosed based on Carpenter and Coustan criteria (SMD: 1.04; 95% CI: 0.42-1.65). Significantly higher MPV also were observed within cross-sectional studies (SMD: 0.99; 95% CI: 0.49-1.49). Remarkable between-study heterogeneity and potential publication bias were observed in this meta-analysis; however, sensitivity analysis indicated that the results were not unduly influenced by any single study. CONCLUSIONS: GDM patients are accompanied by increased MPV, strengthening the clinical evidence that MPV may be a predictive marker for GDM.

Biomineralization-Inspired Synthesis of Cerium-Doped Carbonaceous Nanoparticles for Highly Hydroxyl Radical Scavenging Activity.

Cerium oxide nanoparticles recently have received extensive attention in biomedical applications due to their excellent anti-oxidation performance. In this study, a simple, mild, and green approach was developed to synthesize cerium-doped carbonaceous nanoparticles (Ce-doped CNPs) using bio-mineralization of bull serum albumin (BSA) as precursor. The resultant Ce-doped CNPs exhibited uniform and ultrasmall morphology with an average size of 14.7 nm. XPS and FTIR results revealed the presence of hydrophilic group on the surface of Ce-doped CNPs, which resulted in excellent dispersity in water. The CCK-8 assay demonstrated that Ce-doped CNPs possessed favorable biocompatibility and negligible cytotoxicity. Using H2O2-induced reactive oxygen species (ROS) as model, Ce-doped CNPs showed highly hydroxyl radical scavenging capability. Furthermore, flow cytometry and live-dead staining results indicated that Ce-doped CNPs protected cells from H2O2-induced damage in a dose-dependent effect, which provided a direct evidence for anti-oxidative performance. These findings suggest that Ce-doped CNPs as novel ROS scavengers may provide a potential therapeutic prospect in treating diseases associated with oxidative stress.

Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus.

BACKGROUND: Higher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce. METHODS: 345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured. RESULTS: T2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients. CONCLUSION: Higher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM.

Circulating retinol binding protein 4 levels in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Retinol binding protein 4 (RBP4) is implicated in obesity, insulin resistance and type 2 diabetes mellitus that are closely associated with nonalcoholic fatty liver disease (NAFLD). However, recent investigations regarding circulating RBP4 levels in NAFLD are conflicting. This meta-analysis is to determine whether NAFLD, non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) patients have altered RBP4 levels. METHODS: We performed a systematic search in PubMed, EMBASE and The Cochrane Library up until 18 March 2017, and 12 studies comprising a total of 4247 participants (2271 NAFLD patients and 1976 controls) were included in the meta-analysis. RESULTS: There were no significant differences of circulating RBP4 levels in the following comparisons: (1) NAFLD patients vs controls (standardized mean differences [SMD]: 0.08; 95% CI: -0.21, 0.38); (2) NASH patients vs controls (SMD: -0.49; 95% CI: -1.09, 0.12); (3) SS patients vs controls (SMD: -0.72; 95% CI: -1.64, 0.20) and (4) NASH vs SS patients (SMD: -0.04; 95% CI: -0.32, 0.24). The results remained essentially unchanged in the comparisons between NAFLD patients and controls after excluding single individual study or bariatric studies (n = 2). No significant publication bias was detected. However, there was significant heterogeneity among studies and the subgroup and meta-regression analyses did not find the potential sources. CONCLUSIONS: Circulating RBP4 levels may not be associated with NAFLD. Further prospective cohort studies are required to confirm these findings.

Engineered gadolinium-doped carbon dots for magnetic resonance imaging-guided radiotherapy of tumors.

The effectiveness of radiotherapy can decrease due to inaccurate positioning of machinery and inherent radioresistance of tumors. To address this issue, we present a novel theranostic nanoplatform based on gadolinium-doped carbon dots (Gd-doped CDs) designed specifically for magnetic resonance imaging (MRI)-guided radiotherapy of tumors. The Gd-doped CDs (∼18 nm) with dispersibility in water and stable photoluminescence were synthesized via a one-step hydrothermal approach. After tail vein injection of the Gd-doped CDs, they exhibited a relatively long circulation time (∼6 h), enabled efficient passive tumor targeting. Gd-doped CDs accumulate in the kidney and could be cleared out of the body from bladder. Importantly, they exhibited favorable biocompatibility with excellent performance in longitudinal relaxivity rate (r1) of 6.45 mM-1S-1 and radiosensitization enhancements. These results show that Gd-doped CDs are excellent T1 contrast agents and radiosensitizers, possessing great promise for MRI-guided radiotherapy of tumors.

Effects of combined delivery of extremely low frequency electromagnetic field and magnetic Fe3O4 nanoparticles on hepatic cell lines.

Magnetic Fe3O4 nanoparticles (MNPs) have shown promise as drug carriers for treating lung and liver tumors in vivo. However, little is known about the combined delivery of these MNPs with a second approach, extremely low frequency electro-magnetic field (ELFF) exposure, which has been shown to have value for in vitro treatment of tumor cells. Here, ELFF and MNPs were combined to treat healthy (HL-7702) and cancerous (Bel-7402, HepG2) hepatic cells lines to explore the potential therapeutic effects, bio-mechanisms, and potential toxicity of a combined drug-free treatment in vitro. Flow cytometry for anti-AFP (alpha fetal protein) antibody, which coated the MNPs, indicated that the combined treatment induced Bel-7402 and HepG2 hepatoma cells lines into early apoptosis, without significant effects on healthy hepatic cells. This effect appeared to be mediated through cellular membrane ion metabolism. The presence of AFP-loaded MNPs strengthened the effects of ELFF on tumor cells, inducing a higher frequency of early apoptosis, while having minimal toxic effects on healthy HL-7702 cells. Western blotting revealed that the apoptosis-triggering BCL proteins were up regulated in hepatoma cells compared to healthy cells. Flow cytometry and patch-clamp studies revealed that this resulted from a higher MNP uptake ratio and greater cellular membrane ion exchange current in tumor cells compared to HL-7702 cells. Further, patch-clamp results showed that combining MNPs with ELFF treatment induces cells into early apoptosis through an ion metabolism disturbance in cells, similar to ELFF treatment. In brief, the combination of ELFF and MNPs had beneficial effects on tumor cells without significant toxicity on healthy cells, and these effects were associated with cellular MNP uptake.