This study aimed to evaluate the efficacy and safety of using high-dose intravenous tranexamic acid (TXA) to reduce blood loss in idiopathic scoliosis surgery.
This study was a meta-analysis, which ...consisted of retrospective cohort studies (RCSs) and randomized control trials (RCTs) found by searching electronic databases, namely PubMed, Web of Science, The Cochrane Central Register of Controlled Trials (CENTRAL), and the Google Scholar Database, dating from 1960 to 2019. The points of interest included total blood loss, a need for transfusion and transfusion criteria, surgery time, and the evidence of intraoperative and postoperative complications, such as seizures or thromboembolic events. The weighted mean differences (WMD) and 95% confidence interval (CI) of blood loss in the TXA intervention group compared to the control or placebo group were extracted and combined using the random effects model.
In this meta-analysis, there was a total of three RCSs and two RCTs, which involved 334 patients. The results showed that blood loss is significantly reduced, with a weighted mean difference in the TXA group (WMD = - 525.14, P = 0.0000, CI ranged from - 839.83, - 210.44, I
= 82%). Heterogeneity was assessed using the random effects model.
A high dose of intravenous TXA reduced blood loss during adolescent idiopathic scoliosis surgery and did not lead to any significant thromboembolic event. Therefore, a high dose appears to be effective and safe for adolescent idiopathic scoliosis surgery. However, more high-quality research based on larger randomized controlled trials is still needed.
Flavonoids, which contain a benzo‐γ‐pyrone (C6–C3–C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of ...7,8‐dihydroxyflavone (7,8‐DHF) and 7‐hydroxyflavone (7‐HF) in H2O2, lipopolysaccharide (LPS), or tert‐butyl hydroperoxide (t‐BHP)‐induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8‐DHF and 7‐HF were firstly evaluated by 2,2‐azinobis‐3‐ethyl‐benzothiazoline‐6‐sulphonic acid (ABTS), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2O2, LPS, or t‐BHP‐induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7‐HF and 7,8‐DHF were initially investigated by western blot. Our results showed that 7,8‐DHF possessed stronger free‐radical scavenging capacity than 7‐HF. Both 7,8‐DHF and 7‐HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2O2, LPS, or t‐BHP‐induced RAW264.7 cells, respectively. And 7,8‐DHF exerted a better antioxidant effect than 7‐HF, especially in t‐BHP‐induced oxidative stress. Mechanically, 7,8‐DHF prevented the activation of poly ADP‐ribosepolymerase and caspase‐3, meanwhile markedly upregulated the expression of HO‐1 protein in t‐BHP‐induced oxidative stress. These results suggested that 7,8‐DHF might serve as a potential pharmaceutical drug against oxidative stress injury.
7,8‐dihydroxyflavone exhibited potent antioxidative activity in different experimental systems, and 7,8‐dihydroxyflavone displayed antioxidant effect through activating Heme oxygenase‐1 (HO‐1) expression and inhibiting caspase‐3/poly ADP‐ribosepolymerase activation in RAW264.7 cells.
The design and fabrication of electrocatalysts for HER, with superior activity and stability, still remain a significant challenge for clean and renewable energy technologies. Here we have ...synthesized Fe 3 C/Mo 2 C-containing N, P co-doped graphitic carbon derived from POM@MOF-100 (Fe) (denoted as Fe 3 C/Mo 2 C@NPGC) via a “killing three birds with one stone” strategy. The Fe 3 C/Mo 2 C@NPGC catalyst demonstrates excellent electrocatalytic activity and stability towards HER with a low onset overpotential of 18 mV ( vs. RHE), small Tafel slope of 45.2 mV dec −1 , as well as long-term durability for 10 h, which is one of the best non-noble metal HER catalysts in acidic media reported so far. Most importantly, this work opens up exciting opportunities for fabricating novel and highly efficient electrocatalysts to replace Pt or Pt-based catalysts utilizing POM-based metal–organic frameworks (MOFs) as precursors.
5/6 Nephrectomy (PNx) on rat and mouse mimics renal failure after loss of kidney function in human, and it has been widely used in CKD researches. However, existing methods for PNx model construction ...present high mortality of animals after modeling due to hemorrhage and infection in or after surgery. Here, we report a novel and highly efficient PNx modeling method to simulate conventional 5/6 nephrectomy, which significantly reduced the mortality of animals and simplified the modeling procedures. In this novel modeling method, we directly ligated the upper and lower poles of left kidney after removal the right kidney 1 week later (l-PNx), which leads to necrosis of ligated upper and lower poles of the kidney and mimics the conventional 5/6 nephrectomy (c-PNx). After modeling 4 and 12 weeks, the serum creatinine, BUN and proteinuria levels were strongly increased in both c-PNx and l-PNx model. Importantly, compared with the c-PNx, l-PNx model present more severe renal fibrosis estimated by Masson staining, IHC and western blotting. The results showed that the protein levels of α-SMA were significantly increased in the kidney of c-PNx and l-PNx models, but more increase was found in l-PNx model. It is noteworthy that, compared with c-PNx model, the survival rate of l-PNx model was markedly increased. In summary, we established a novel and efficient 5/6 nephrectomy model, which can mimic conventional 5/6 nephrectomy to construct a renal fibrosis and renal failure mouse model, that is conducive to mechanism and treatment researches of CKD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis and hepatocyte injury, is an obesity-induced metabolic dysregulation with few available therapeutic options. Enhancement ...of the mitochondrial function was considered as an effective treatment for NALFD. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on metabolic syndrome disease such as hyperlipidemia, coronary artery disease and cardiovascular diseases. The seed oil of Rosa roxburghii Tratt (ORRT) was of high quality in terms of its high amount of unsaturated fatty acids. However, the effects of ORRT on NALFD have not been reported so far.
The study aimed to evaluate the protective effects and molecular mechanism of ORRT for the treatment of NAFLD in vivo and in vitro.
The beneficial effects, especially improving the mitochondrial function, and the potential mechanism of ORRT on NAFLD were studied both in vivo and in vitro. Lipid levels were determined by triglyceride (TG), total cholesterol (TC), and Oil Red O staining. Oxidative stress and inflammation were assessed by detecting antioxidant enzyme activity, MDA content, and ELISA assay. Blood TG, TC, HDL-c and LDL-c levels were measured in HFD mice. Western blot analyses were used to determine the levels of the protein involved in fatty acid oxidation, oxidative metabolism, and mitochondria biogenesis and function. The mitochondrial membrane potential level was measured by JC-1 staining to teste the effect of ORRT on mitochondrial function in vitro. GW6471 (inhibitor of PPARα) was used to confirm the relationship between PPARα and PGC-1α.
ORRT significantly restrained NAFLD progression by attenuating lipid accumulation, oxidative stress and inflammatory response. Furthermore, ORRT upregulated thermogenesis-related gene expressions, such as uncoupling protein 1 (UCP1) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that the expression of key genes involved in fatty acid oxidation (e.g., CPT-1α, ACADL, PPARα) and in mitochondrial biogenesis and function (e.g., TFAM, NRF1, PGC-1α, and COX IV) was significantly increased. Together with the observed MMP improvement, these findings suggested that ORRT activated the mitochondrial oxidative pathway. Additionally, GW6471 inhibited the ORRT on promoting the expression of PGC-1α, CPT-1α, and ACADL. In conclusion, ORRT possessed the potential to prevent lipid accumulation via the PPARα/PGC-1α signaling pathway, which could be developed as a natural health-promoting oil against NAFLD.
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Abstract
The effects of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) on tumor cells and the relevant mechanisms are less well defined. This study aimed to explore the ...role and mechanism of action of NUCKS1 in gastric cancer (GC) progression. The expression dynamics of NUCKS1 were examined using microarray-based immunohistochemistry (IHC) in a group of carcinomatous and adjacent non-tumor specimens. Various in vitro and in vivo assays were performed to clarify the function of NUCKS1 in GC and its underlying mechanisms. In our research, NUCKS1 overexpression was identified by IHC in 86/200 (43%) GC patients, was significantly related to the invasive phenotype of GC and was an indisputable predictor of shortened survival. Depleting NUCKS1 in GC cells significantly induced apoptosis and reduced cell proliferation and invasiveness in vitro and inhibited tumor growth in vivo. Additionally, ectopic overexpression of NUCKS1 in GC cells enhanced proliferation and invasion in vitro and promoted tumor growth in vivo. Importantly, PI3K/Akt/mTOR signaling pathway activity was inhibited upon downregulation of NUCKS1 expression and enhanced by ectopic overexpression of NUCKS1. Subsequently, the insulin-like growth factor 1 receptor (IGF-1R) gene was found to be a potential downstream target of NUCKS1 in GC cells, and knockdown of IGF-1R eliminated the augmentation of GC cell migration, invasion and proliferation as well as PI3K/Akt/mTOR signaling pathway activity by ectopic NUCKS1. The data suggested that NUCKS1 enhanced GC aggressiveness via the PI3K/Akt/mTOR signaling pathway in an IGF-1R-dependent manner. NUCKS1 or its respective signaling pathways could hold immense promise as potent anticancer targets for GC treatment.
Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the
...gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the
gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots.
expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava.
expression patterns were further confirmed in
transgenic cassava. The promoter deletion analysis showed that the -264 bp to -1 bp
promoter has basal activity. The range from -1228 bp to -987 bp and -488 bp to -264 bp significantly enhance promoter activity. The regions from -987 bp to -747 bp and -747 bp to -488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the
gene and for further in-depth exploration of the regulatory network of its internal functional elements.
According to the World Health Organization (WHO), gastric cancer (GC) is the fourth leading cause of tumor-related mortality globally and one of the most prevalent malignant tumors. To better ...understand the role of tumor-infiltrating B cells (TIBs) in GC, this work used single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data to identify candidate hub genes. Both scRNA-Seq and bulk RNA-Seq data for stomach adenocarcinoma (STAD) were obtained from the GEO and TCGA databases, respectively. Using scRNA-seq data, the FindNeighbors and FindClusters tools were used to group the cells into distinct groups. Immune cell clusters were sought in the massive RNA-seq expression matrix using the single-sample gene set enrichment analysis (ssGSEA). The expression profiles were used in Weighted Gene Coexpression Network Analysis (WGCNA) to build TCGA’s gene coexpression networks. Next, univariate Cox regression, LASSO regression, and Kaplan–Meier analyses were used to identify hub genes in scRNA-seq data from sequential B-cell analyses. Finally, we examined the correlation between the hub genes and TIBs utilizing the TISIDB database. We confirmed the immune-related markers in clinical validation samples using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). 15 cell clusters were classified in the scRNA-seq database. According to the WGCNA findings, the green module is most associated with cancer and B cells. The intersection of 12 genes in two separate datasets (scRNA and bulk) was attained for further analysis. However, survival studies revealed that increased C-X-C motif chemokine receptor 4 (CXCR4) expression was linked to worse overall survival. CXCR4 expression is correlated with active, immature, and memory B cells in STAD were identified. Finally, RT-PCR and IHC assays verified that in GC, CXCR4 is overexpressed, and its expression level correlates with TIBs. We used scRNA-Seq and bulk RNA-Seq to study STAD’s cellular composition. We found that CXCR4 is highly expressed by TIBs in GC, suggesting that it may serve as a hub gene for these cells and a starting point for future research into the molecular mechanisms by which these immune cells gain access to tumors and potentially identify therapeutic targets.
Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR ...tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.
Organic pollutants, including mycotoxins, organic dyes, and pesticide residues, are the most critical threats to the global environment. In particular, efficient adsorption based on synthetic ...nanomaterials is considered a versatile and green approach to control mycotoxins. This work systematically investigates the aflatoxin B1 (AFB1) removal capacity of MIL‐101(Fe), a typical type of metal‐organic framework (MOF) synthesized by solvothermal methods and possesses super‐high porosity and excellent dispersion in liquid. The experimental results demonstrate that as‐prepared MIL‐101(Fe) exhibits a much higher saturated loading capacity (30.58 mg g−1) toward AFB1 than other adsorbents described in the literature. Subsequently, the adsorption process is studied via isothermal and kinetic analyses. This work also evaluates the removal effect of MIL‐101(Fe) on organic dyes and pesticides compared to the other five MOFs; the results reveal that MIL‐101(Fe) possesses a diversity of pollutant adsorption. The molecular docking and interaction region indicator analysis is applied to reflect the interactions between AFB1 molecules and MIL‐101(Fe). This work will provide a simple and effective approach for AFB1 treatment and adsorption in wastewaters and offer new insights and perspectives to the practical applications of synthetic nanomaterials, MOFs in environmental management.
Functional MIL‐101(Fe) and hydrophobic chlorotrimethylsilane‐MIL‐101 are prepared and applied as high‐efficiency adsorbents to remove the malignant mycotoxin aflatoxin B1 (AFB1) in different liquids. Molecular docking and computational chemistry are used to elucidate the adsorption model of MIL‐101 on AFB1 and reveal their microcosmic interaction mechanism.
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