Our meta-analysis aims to investigate the prognostic role of pretreatment albumin to globulin ratio (AGR) in human cancers.
Available databases were searched up to Sept 25th, 2017. Pooled hazard ...ratios (HRs) and risk ratio (RRs) with their corresponding 95% confidence intervals (CIs) were used to assess the prognostic impact of AGR on overall survival (OS)/disease-free survival (DFS)/progression-free survival (PFS) and 5-year mortality respectively.
Totally, 28 studies with 15 356 cancer patients were included. Our results demonstrated that low pretreatment AGR is associated with poor OS (HR=2.08, 95%CI:1.78–2.44, univariate results; HR=1.75, 95%CI:1.56–1.97, multivariate results), poor DFS (HR=1.96, 95%CI:1.48–2.59, univariate results; HR=1.64, 95%CI:1.26–2.14, multivariate results) and poor PFS (HR=1.89, 95%CI:1.61–2.22, univariate results; HR=1.66, 95%CI:1.32–2.0, multivariate results). Meanwhile, low pretreatment AGR is also associated with increased 5-year mortality (RR=2.12, 95%CI:1.48–3.03). Moreover, this significant correlation was not altered by stratified analysis according to publication times, sample sizes, patient origins, AGR cutoff values, cancer systems, treatment methods or HR sources.
Low pretreatment AGR is associated with poor prognosis in human cancers, and AGR should be used as a prognostic marker during cancer therapy.
•A meta-analysis investigated the prognostic value of AGR on cancers.•28 studies with 15 356 cancer patients were included in this meta-analysis.•Low pretreatment AGR is associated with poor prognosis in human cancers.•Pretreatment AGR should be used as a prognostic marker during cancer therapy.
Osteoarthritis (OA) is a progressive joint disorder that is primarily characterized by the degeneration and destruction of the articular cartilage. Cartilage matrix degradation, production of ...proinflammatory mediators, chondrocyte apoptosis and activation of macrophages in the synovial are involved in OA pathogenesis. Current non-surgical therapies for OA mainly aim at relieving pain but can barely alleviate the progression of OA. Quercetin, a naturally occurring flavonoid has shown potent anti-inflammatory effects, however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we explored the protective effects of quercetin on repairing OA-induced cartilage injuries and its possible mechanisms. In vitro, quercetin remarkably suppressed the expression of matrix degrading proteases and inflammatory mediators, meantime promoted the production of cartilage anabolic factors in interleukin-1β-induced (IL-1β) rat chondrocytes. In addition, quercetin exhibited anti-apoptotic effects by decreasing intracellular reactive oxygen species (ROS), restoring mitochondrial membrane potential (MMP) and inhibiting the Caspase-3 pathway in apoptotic rat chondrocytes. Moreover, quercetin induced M2 polarization of macrophages and upregulated the expression of transforming growth factor β (TGF-β) and insulin-like growth factor (IGF), which in turn created a pro-chondrogenic microenvironment for chondrocytes and promoted the synthesis of glycosaminoglycan (GAG) in chondrocytes. In vivo, intra-articular injection of quercetin alleviated the degradation of the cartilage and the apoptosis of chondrocytes in a rat OA model. Moreover, the expression of TGF-β1 and TGF-β2 in the synovial fluid and the ratio of M2 macrophages in the synovial membrane were elevated. In summary, our study proves that quercetin exerts chondroprotective effects by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages and creating a pro-chondrogenic environment for chondrocytes to enhance cartilage repair under OA environment. It is suggested that quercetin may serve as a potential drug for OA treatment.
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•Quercetin exerted anti-inflammatory effects on IL-1β-induced rat chondrocytes by inhibiting the Akt/NF-κB signaling pathway.•Quercetin attenuated chondrocytes apoptosis by inhibiting the Caspase-3 pathway via decreasing overproduction of the intracellular ROS and restoring mitochondrial membrane potential.•Quercetin exerted immunomodulatory effect in modulating synovial macrophages polarization to M2 macrophages which forms a pro-chondrogenic microenvironment for chondrocytes and promotes cartilage repair.•An intra-articular injection of quercetin could attenuate OA in a rat OA model.
The effects of body mass index (BMI) on the prognosis of acute respiratory distress syndrome (ARDS) are controversial. We aimed to further determine the relationship between BMI and the acute ...outcomes of patients with ARDS.
We searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and ISI Web of Science for trials published between 1946 and July 2016, using "BMI" or "body mass index" or "overweight" or "obese" and "ARDS" or "ALI" or "acute respiratory distress syndrome" or "acute lung injury", without limitations on publication type or language. Heterogeneity and sensitivity analyses were conducted, and a random-effects model was applied to calculate the odds ratio (OR) or mean difference (MD). Review Manager (RevMan) was used to test the hypothesis using the Mann-Whitney U test. The primary outcome was unadjusted mortality, and secondary outcomes included mechanical ventilation (MV)-free days and length of stay (LOS) in the intensive care unit (ICU) and in hospital.
Five trials with a total of 6268 patients were pooled in our final analysis. There was statistical heterogeneity between normal-weight and overweight patients in LOS in the ICU (I
= 71%, χ
= 10.27, P = 0.02) and in MV-free days (I
= 89%, χ
= 18.45, P < 0.0001). Compared with normal weight, being underweight was associated with higher mortality (OR 1.59, 95% confidence interval (CI) 1.22, 2.08, P = 0.0006), while obesity and morbid obesity were more likely to result in lower mortality (OR 0.68, 95% CI 0.57, 0.80, P < 0.00001; OR 0.72, 95% CI 0.56, 0.93, P = 0.01). MV-free days were much longer in patients with morbid obesity (MD 2.64, 95% CI 0.60, 4.67, P = 0.01), but ICU and hospital LOS were not influenced by BMI. An important limitation of our analysis is the lack of adjustment for age, sex, illness severity, comorbid illness, and interaction of outcome parameters.
Obesity and morbid obesity are associated with lower mortality in patients with ARDS.
Mendelian randomization is a statistical method for inferring the causal relationship between exposures and outcomes using an economics‐derived instrumental variable approach. The research results ...are relatively complete when both exposures and outcomes are continuous variables. However, due to the noncollapsing nature of the logistic model, the existing methods inherited from the linear model for exploring binary outcome cannot take the effect of confounding factors into account, which leads to biased estimate of the causal effect. In this article, we propose an integrated likelihood method MR‐BOIL to investigate causal relationships for binary outcomes by treating confounders as latent variables in one‐sample Mendelian randomization. Under the assumption of a joint normal distribution of the confounders, we use expectation maximization algorithm to estimate the causal effect. Extensive simulations demonstrate that the estimator of MR‐BOIL is asymptotically unbiased and that our method improves statistical power without inflating type I error rate. We then apply this method to analyze the data from Atherosclerosis Risk in Communications Study. The results show that MR‐BOIL can better identify plausible causal relationships with high reliability, compared with the unreliable results of existing methods. MR‐BOIL is implemented in R and the corresponding R code is provided for free download.
Poisoning is a leading cause of admission to medical emergency departments and intensive care units. Supramolecular detoxification, which involves injecting supramolecular receptors that bind with ...toxins to suppress their biological activity, is an emerging strategy for poisoning treatment; it has few requirements and a broad application scope. However, it is still a formidable challenge to design supramolecular therapeutic materials as an antidote to macromolecular toxins, because the large size, flexible conformation, and presence of multiple and diverse binding sites of biomacromolecules hinder their recognition. Herein, a supramolecular antidote to macromolecular toxins is developed through the coassembly of macrocyclic amphiphiles, relying on heteromultivalent recognition between the coassembled components and toxic macromolecules. The coassembly of amphiphilic cyclodextrin and calixarene strongly and selectively captures melittin, a toxin studied herein; this imparts various therapeutic effects such as inhibiting the interactions of melittin with cell membranes, alleviating melittin cytotoxicity and hemolytic toxicity, reducing the mortality rate of melittin‐poisoned mice, and mitigating damage to major organs. The use of the proposed antidote overcomes the limitation of supramolecular detoxification applicability to only small‐molecular toxins. The antidote can also detoxify other macromolecular toxins as long as selective and strong binding is achieved because of the coassembling tunability.
Supramolecular detoxification is an emerging strategy for treating poisoning; however, developing supramolecular therapeutic materials as an antidote to macromolecular toxins is challenging. To overcome this challenge, a heteromultivalent coassembling material (CCA‐CD) comprising macrocyclic amphiphiles is developed. The CCA‐CD binds with melittin strongly and selectively, and significantly alleviates its toxicity, serving as a novel supramolecular antidote used for melittin poisoning treatment.
Rapid acquisition of the spatial distribution of soil nutrients holds great implications for farmland soil productivity safety, food security and agricultural management. To this end, we collected ...1297 soil samples and measured the content of soil total nitrogen (TN), soil available phosphorus (AP) and soil available potassium (AK) in Zengcheng, north of the Pearl River Delta, China. Hyperspectral remote sensing images (115 bands) of the Chinese Environmental 1A satellite were used as auxiliary variables and dimensionality reduction was performed using Pearson correlation analysis and principal component analysis. The TN, AP and AK of soil were predicted in the study area based on auxiliary variables after dimensionality reduction, along with stepwise linear regression (SLR), support vector machine (SVM), random forest (RF) and back-propagation neural network (BPNN) models; 324 independent points were used to verify the predictive performance. The BPNN model, which demonstrated the best predictive accuracy among all methods, combined ordinary kriging (OK) with mapping the spatial variations of soil nutrients. Results show that the BPNN model with double hidden layers had better predictive accuracy for soil TN (root mean square error (
) = 0.409 mg kg
,
² = 44.24%), soil AP (
= 40.808 mg kg
,
² = 42.91%) and soil AK (
= 67.464 mg kg
,
² = 48.53%) compared with the SLR, SVM and RF models. The back propagation neural network-ordinary kriging (BPNNOK) model showed the best predictive results of soil TN (
= 0.292 mg kg
,
² = 68.51%), soil AP (
= 29.62 mg kg
,
² = 69.30%) and soil AK (
= 49.67 mg kg
and
² = 70.55%), indicating the best fitting ability between hyperspectral remote sensing bands and soil nutrients. According to the spatial mapping results of the BPNNOK model, concentrations of soil TN (north-central), soil AP (central and southwest) and soil AK (central and southeast) were respectively higher in the study area. The most important bands (464⁻517 nm) for soil TN (b10, b14, b20 and b21), soil AP (b3, b19 and b22) and soil AK (b4, b11, b12 and b25) exhibited the best response and sensitivity according to the SLR, SVM, RF and BPNN models. It was concluded that the application of hyperspectral images (visible-near-infrared data) with BPNNOK model was found to be an efficient method for mapping and monitoring soil nutrients at the regional scale.
Macrocyclic delivery and therapeutics are two significant topics in supramolecular biomedicine. The functional integration of these topics would open new avenues for treating diseases ...synergistically. However, these two individual topics have only been occasionally merged, probably because of the lack of functionalized design of macrocyclic host and the lack of efficient recognition between host and guest drugs. Herein, a “drug‐in‐drug” strategy is proposed, in which an active drug is encapsulated by a macrocycle possessing therapeutic activity to form a multifunctional supramolecular active pharmaceutical ingredient. As a proof‐of‐concept, a complex of hydroxychloroquine (HCQ) with sulfonated azocalix4arene (HCQ@SAC4A) is prepared to treat rheumatoid arthritis (RA) in a combined fashion. SAC4A is a therapeutic agent that exhibits scavenging capacity for reactive oxygen species and exerts an anti‐inflammatory effect. It is also a hypoxia‐responsive carrier that can deliver HCQ directly to the inflammatory articular cavity. Consequently, HCQ@SAC4A achieves the synergistic anti‐inflammatory effect on both inflamed RAW 264.7 cells and RA rats. This effect is attributed to the temporal and spatial consistency of the two active ingredients of the complex. As a new paradigm for combinational therapy, the drug‐in‐drug strategy advances in easy preparation, mix‐and‐match combination, and precise ratiometric control.
Macrocyclic delivery and therapeutics are two hotspots in supramolecular biomedicine that have only been occasionally merged. In this work, a “drug‐in‐drug” strategy is proposed, in which an active drug is encapsulated by a therapeutically active macrocycle, forming a multifunctional supramolecular active ingredient. This drug‐in‐drug formulation achieves the advantages of macrocycles acting as both carriers and therapeutic agents to realize combinational therapy.
Background
Ovarian cancer is one of the three major malignant tumors of the female reproductive system, and the mortality associated with ovarian cancer ranks first among gynecologic malignant ...tumors. The pathogenesis of ovarian cancer is not yet clearly defined but elucidating this process would be of great significance for clinical diagnosis, prevention, and treatment. For this study, we used bioinformatics to identify the key pathogenic genes and reveal the potential molecular mechanisms of ovarian cancer; we used immunohistochemistry to validate them.
Methods
We analyzed and integrated four gene expression profiles (GSE14407, GSE18520, GSE26712, and GSE54388), which were downloaded from the Gene Expression Omnibus (GEO) database, with the aim of obtaining a common differentially expressed gene (DEG). Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We then established a protein–protein interaction (PPI) network of the DEGs through the Search Tool for the Retrieval of Interacting Genes (STRING) database and selected hub genes. Finally, survival analysis of the hub genes was performed using a Kmplotter online tool.
Results
A total of 226 DEGs were detected after the analysis of the four gene expression profiles; of these, 87 were upregulated genes and 139 were downregulated. GO analysis results showed that DEGs were significantly enriched in biological processes including the G2/M transition of the mitotic cell cycle, the apoptotic process, cell proliferation, blood coagulation, and positive regulation of the canonical Wnt signaling pathway. KEGG analysis results showed that DEGs were particularly enriched in the cell cycle, the p53 signaling pathway, the Wnt signaling pathway, the Ras signaling pathway, the Rap1 signaling pathway, and tyrosine metabolism. We selected 50 hub genes from the PPI network, which had 147 nodes and 655 edges, and 30 of them were associated with the prognosis of ovarian cancer. We performed immunohistochemistry on phosphoserine aminotransferase 1 (PSAT1). PSAT1 was highly expressed in cancer tissues, and its expression level was related to clinical stage and tissue differentiation in ovarian cancer. A Cox proportional risk model suggested that high expression of PSAT1 and late clinical stage were independent risk factors for survival and prognosis of ovarian cancer patients.
Conclusion
The detection of DEGs using bioinformatics analysis might be crucial to understanding the pathogenesis of ovarian cancer, especially the molecular mechanisms of its development. The association between PSAT1 expression and the occurrence, development, and prognosis of ovarian cancer was further verified by immunohistochemistry. The PSAT1 expression can be used as a prognostic marker to provide a potential target for the diagnosis and treatment of ovarian cancer.
We used bioinformatics methods to integrate multiple ovarian cancer data sets in the Gene Expression Omnibus database to find core genes involved in the development of ovarian cancer. The Kaplan–Meier plotter and Oncomine databases were used to verify the prognosis and expression of the research gene phosphoserine aminotransferase 1 (PSAT1). The expression of PSAT1 in ovarian cancer was further verified by immunohistochemistry and its relationships with clinical pathological parameters and survival prognosis of ovarian cancer were analyzed. PSAT1 expression associates with distinct patterns of genomic alterations and biological process were performed to explore the possible mechanisms of PSAT1 in tumorigenesis. In future studies, we will further verify the biological behavior and molecular mechanism of PSAT1 in ovarian cancer cells by cytology experiments.
Organometal lead halide perovskites have been widely used as the light harvester for high-performance solar cells. However, typical perovskites of methylammonium lead halides (CH
NH
PbX
, X=Cl, Br, ...I) are usually sensitive to moisture in ambient air, and thus require an inert atmosphere to process. Here we demonstrate a moisture-induced transformation of perovskite crystals in a triple-layer scaffold of TiO
/ZrO
/Carbon to fabricate printable mesoscopic solar cells. An additive of ammonium chloride (NH
Cl) is employed to assist the crystallization of perovskite, wherein the formation and transition of intermediate CH
NH
X·NH
PbX
(H
O)
(X=I or Cl) enables high-quality perovskite CH
NH
PbI
crystals with preferential growth orientation. Correspondingly, the intrinsic perovskite devices based on CH
NH
PbI
achieve an efficiency of 15.6% and a lifetime of over 130 days in ambient condition with 30% relative humidity. This ambient-processed printable perovskite solar cell provides a promising prospect for mass production, and will promote the development of perovskite-based photovoltaics.
Metabolic reprogramming plays a critical role in many diseases. A recent study revealed that aerobic glycolysis in lung tissue is closely related to pulmonary fibrosis, and also occurs during ...lipopolysaccharide (LPS)-induced sepsis. However, whether LPS induces aerobic glycolysis in lung fibroblasts remains unknown. The present study demonstrated that LPS promotes collagen synthesis in the lung fibroblasts through aerobic glycolysis via the activation of the PI3K-Akt-mTOR/PFKFB3 pathway. Challenging the human lung fibroblast MRC-5 cell line with LPS activated the PI3K-Akt-mTOR pathway, significantly upregulated the expression of 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), enhanced the aerobic glycolysis, and promoted collagen synthesis. These phenomena could be reversed by the PI3K-Akt inhibitor LY294002, mTOR inhibitor rapamycin, PFKFB3 inhibitor 3PO, or PFKFB3 silencing by specific shRNA, or aerobic glycolysis inhibitor 2-DG. In addition, PFKFB3 expression and aerobic glycolysis were also detected in the mouse model of LPS-induced pulmonary fibrosis, which could be reversed by the intraperitoneal injection of PFKFB3 inhibitor 3PO. Taken together, this study revealed that in LPS-induced pulmonary fibrosis, LPS might mediate lung fibroblast aerobic glycolysis through the activation of the PI3K-Akt-mTOR/PFKFB3 pathway.
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