scholarly journals Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258187
Author(s):  
David Z. Allen ◽  
Jihad Aljabban ◽  
Dustin Silverman ◽  
Sean McDermott ◽  
Ross A. Wanner ◽  
...  

Background Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies. Methods We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples. Results Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3. Conclusions Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 71-71
Author(s):  
Kamal Khorfan ◽  
Jihad Aljabban ◽  
Saad Syed ◽  
Hussam Salhi ◽  
Aderinola Adejare ◽  
...  

71 Background: Esophageal adenocarcinoma (EAC) is the sixth most common cause of cancer-related deaths worldwide. It commonly arises in the setting of reflux disease and Barett’s esophagus. It remains incurable and holds a poor prognosis. Dissecting the genetic signature of EAC can pave new therapeutic avenues. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO). We tagged 151 tumor samples from EAC patients and 62 normal esophageal samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between tumor and control. Results: Our analysis revealed granulocyte adhesion and diapedesis and FXR/RXR signaling as top canonical pathways. TGFB1, TNF, and beta-estradiol were top upstream regulators with predicted activation. TGFB1 and TNF expression have been correlated with poor prognosis in EAC. Also, beta-estradiol has tumorigenic activity in several cancers but has not been investigated in EAC. Among the top upregulated genes were oncogenic genes such as tetraspanin 8, the antiapoptotic factor OLFM4, and the protease cathepsin E (CTSE). SPINK1, a trypsin inhibitor with recently suggested role in cancer, and the choline transporter SLC44A4, a drug target for pancreatic cancer, were also upregulated. The most downregulated genes included alcohol dehydrogenase 7, associated with EAC in alcohol-drinkers, and the pro-apoptotic gene CRCT1. We also found downregulation of the serine peptidase inhibitor SPINK7. SPINK7 is involved in maintaining epithelial-barrier integrity and is implicated in eosinophilic esophagitis pathogenesis. Lastly, there was downregulation of the candidate tumor suppressor gene transglutaminase 3. Conclusions: Despite screening efforts, EAC incidence and mortality continues to increase as does the need for better treatment. This meta-analysis defines the significant gene expression changes within causal disease processes to provide markers for detection, prognostic insight, and therapeutic value for EAC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Anji Xiong ◽  
Chen Xiong ◽  
Guancui Yang ◽  
Yu Shuai ◽  
Deng Liu ◽  
...  

Objectives: The successful introduction of mycophenolate mofetil (MMF) as a treatment for renal allograft reduced the incidence of acute rejection. The inspiring effects obtained by the MMF have led to an evaluation of its therapeutic potency on ANCA-associated vasculitis (AAV). However, there is little evidence of the MMF's efficacy on the AAV. The meta-analysis is carried out to evaluate the efficacy of MMF as a remission induction therapy in AAV.Methods: Up to June 30th, 2020, PubMed, Cochrane Library, and Embase have been searched comprehensively. According to heterogeneity, the pooled remission rates are synthesized by either fixed-effect or random-effect models.Results: The eight included studies comprising 230 patients who were treated with MMF as induction therapy are included in our analysis. The pooled overall remission rate is 74% (95% CI: 0.68–0.80). The remission rate, the infection rate and the rate of leukopenia of four randomized controlled trials aimed at comparing the effects of MMF with cyclophosphamide (CYC) during induction therapy for AAV have no statistical significance (P &gt; 0.05).Conclusion: MMF may be an alternative to CYC for remission induction therapy in AAV with MPO-ANCA, mild to moderate renal involvement and non-life-threatening state. Whether to observe the effect of MMF in AAV or to compare the difference between MMF and CYC in the future studies, risk stratification and subgrouping of AAV patients should be first carried out to correctly identify the AAV subgroup suitable for MMF.


2020 ◽  
Vol 26 (29) ◽  
pp. 3619-3630
Author(s):  
Saumya Choudhary ◽  
Dibyabhaba Pradhan ◽  
Noor S. Khan ◽  
Harpreet Singh ◽  
George Thomas ◽  
...  

Background: Psoriasis is a chronic immune mediated skin disorder with global prevalence of 0.2- 11.4%. Despite rare mortality, the severity of the disease could be understood by the accompanying comorbidities, that has even led to psychological problems among several patients. The cause and the disease mechanism still remain elusive. Objective: To identify potential therapeutic targets and affecting pathways for better insight of the disease pathogenesis. Method: The gene expression profile GSE13355 and GSE14905 were retrieved from NCBI, Gene Expression Omnibus database. The GEO profiles were integrated and the DEGs of lesional and non-lesional psoriasis skin were identified using the affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes pathways of the DEGs were analyzed using clusterProfiler. Cytoscape, V3.7.1 was utilized to construct protein interaction network and analyze the interactome map of candidate proteins encoded in DEGs. Functionally relevant clusters were detected through Cytohubba and MCODE. Results: A total of 1013 genes were differentially expressed in lesional skin of which 557 were upregulated and 456 were downregulated. Seven dysregulated genes were extracted in non-lesional skin. The disease gene network of these DEGs revealed 75 newly identified differentially expressed gene that might have a role in development and progression of the disease. GO analysis revealed keratinocyte differentiation and positive regulation of cytokine production to be the most enriched biological process and molecular function. Cytokines -cytokine receptor was the most enriched pathways. Among 1013 identified DEGs in lesional group, 36 DEGs were found to have altered genetic signature including IL1B and STAT3 which are also reported as hub genes. CCNB1, CCNA2, CDK1, IL1B, CXCL8, MKI 67, ESR1, UBE2C, STAT1 and STAT3 were top 10 hub gene. Conclusion: The hub genes, genomic altered DEGs and other newly identified differentially dysregulated genes would improve our understanding of psoriasis pathogenesis, moreover, the hub genes could be explored as potential therapeutic targets for psoriasis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María Isabel Iñiguez-Luna ◽  
Jorge Cadena-Iñiguez ◽  
Ramón Marcos Soto-Hernández ◽  
Francisco Javier Morales-Flores ◽  
Moisés Cortes-Cruz ◽  
...  

AbstractBioprospecting identifies new sources of compounds with actual or potential economic value that come from biodiversity. An analysis was performed regarding bioprospecting purposes in ten genotypes of Sechium spp., through a meta-analysis of 20 information sources considering different variables: five morphological, 19 biochemical, anti-proliferative activity of extracts on five malignant cell lines, and 188 polymorphic bands of amplified fragment length polymorphisms, were used in order to identify the most relevant variables for the design of genetic interbreeding. Significant relationships between morphological and biochemical characters and anti-proliferative activity in cell lines were obtained, with five principal components for principal component analysis (SAS/ETS); variables were identified with a statistical significance (< 0.7 and Pearson values ≥ 0.7), with 80.81% of the accumulation of genetic variation and 110 genetic bands. Thirty-nine (39) variables were recovered using NTSYSpc software where 30 showed a Pearson correlation (> 0.5) and nine variables (< 0.05), Finally, using a cladistics analysis approach highlighted 65 genetic bands, in addition to color of the fruit, presence of thorns, bitter flavor, piriform and oblong shape, and also content of chlorophylls a and b, presence of cucurbitacins, and the IC50 effect of chayote extracts on the four cell lines.


Vascular ◽  
2021 ◽  
pp. 170853812199127
Author(s):  
Lixin Wang ◽  
Enci Wang ◽  
Fei Liu ◽  
Wei Zhang ◽  
Xiaolong Shu ◽  
...  

Objective This systematic review and meta-analysis evaluated the published data on the efficacy and safety of therapies for superior mesenteric venous thrombosis (SMVT), aiming to provide a reference and set of recommendations for clinical treatment. Methods Relevant databases were searched for studies published from 2000 to June 2020 on SMVT treated with conservative treatment, surgical treatment, or endovascular approach. Different treatment types were grouped for analysis and comparison, and odds ratios with corresponding 95% confidence intervals were calculated. The outcomes were pooled using meta-analytic methods and presented by forest plots. Results Eighteen articles, including eight on SMVT patients treated with endovascular therapies, were enrolled. The treatment effectiveness was compared between different groups according to the change of symptoms, the occurrence of complications, and mortality as well. The conservative treatment group had better efficacy compared to the surgery group (89.0% vs. 78.6%, P <0.05), and the one-year survival rate was also higher (94.4% vs. 80.0%, P >0.05), but without statistical significance. As for endovascular treatment, the effectiveness was significantly higher than the surgery group (94.8% vs. 75.2%, P <0.05), and the conservative treatment group as well (93.3% vs. 86.3%, P >0.05), which still requires further research for the lack of statistical significance. Conclusions Present findings indicate that anticoagulation, as conservative treatment should be the preferred clinical option in the clinic for SMVT, due to its better curative effect compared to other treatment options, including lower mortality, fewer complications, and better prognosis. Moreover, endovascular treatment is a feasible and promising approach that is worth in-depth research, for it is less invasive than surgery and has relatively better effectiveness, thus can provide an alternative option for SMVT treatment and may be considered as a reliable method in clinical.


2021 ◽  
Vol 11 (7) ◽  
pp. 677
Author(s):  
Jeong Yee ◽  
Hamin Kim ◽  
Yunhee Heo ◽  
Ha-Young Yoon ◽  
Gonjin Song ◽  
...  

Purpose: Cytochrome P450 (CYP) is involved in the metabolism of statins; CYP3A5 is the main enzyme responsible for lipophilic statin metabolism. However, the evidence of the association between CYP3A5*3 polymorphism and the risk of statin-induced adverse events remains unclear. Therefore, this study aimed to perform a systematic review and meta-analysis to investigate the relationship between the CYP3A5*3 polymorphism and the risk of statin-induced adverse events. Methods: The PubMed, Web of Science, and EMBASE databases were searched for qualified studies published until August 2020. Observational studies that included the association between statin-induced adverse events and the CYP3A5*3 polymorphism were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated to assess the strength of the relationship. The Mantel–Haenszel method was used to provide the pooled ORs. Heterogeneity was estimated with I2 statistics and publication bias was determined by Begg’s and Egger’s test of the funnel plot. Data analysis was performed using Review Manager (version 5.4) and R Studio (version 3.6). Results: In total, data from 8 studies involving 1614 patients were included in this meta-analysis. The CYP3A5*3 polymorphism was found to be associated with the risk of statin-induced adverse events (*3/*3 vs. *1/*1 + *1/*3: OR = 1.40, 95% CI = 1.08–1.82). For myopathy, the pooled OR was 1.30 (95% CI: 0.96–1.75). The subgroup analysis of statin-induced myopathy revealed a trend, which did not achieve statistical significance. Conclusions: This meta-analysis demonstrated that the CYP3A5*3 polymorphism affected statin-induced adverse event risk. Therefore, CYP3A5 genotyping may be useful to predict statin toxicity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Klementina Ocskay ◽  
Anna Kanjo ◽  
Noémi Gede ◽  
Zsolt Szakács ◽  
Gabriella Pár ◽  
...  

Abstract Background The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. Methods The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). Results In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6–0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. Conclusion PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.


Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090235
Author(s):  
Shih-Wei Lai ◽  
Cheng-Chan Yu ◽  
Cheng-Li Lin ◽  
Kuan-Fu Liao

Background/Objective: Some case series and case report have shown the association between the risk of acute pancreatitis and use of selective serotonin reuptake inhibitors. The results of systematic studies were not consistent. Methods: A meta-analysis was performed to investigate the risk of acute pancreatitis associated with use of selective serotonin reuptake inhibitors. Results: There was no statistical association between the risk of acute pancreatitis and selective serotonin reuptake inhibitors use (odds ratio: 1.19, 95% confidence interval: 0.93-1.51). Conclusions: Despite reaching no statistical significance, the possibility of the association between the risk of acute pancreatitis and selective serotonin reuptake inhibitors use cannot be totally excluded.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James M. Brimson ◽  
Sirikalaya Brimson ◽  
Mani Iyer Prasanth ◽  
Premrutai Thitilertdecha ◽  
Dicson Sheeja Malar ◽  
...  

AbstractBacopamonnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and ‘n’ numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer’s disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 404
Author(s):  
Emma Altobelli ◽  
Paolo Matteo Angeletti ◽  
Ciro Marziliano ◽  
Marianna Mastrodomenico ◽  
Anna Rita Giuliani ◽  
...  

Diabetes mellitus is an important issue for public health, and it is growing in the world. In recent years, there has been a growing research interest on efficacy evidence of the curcumin use in the regulation of glycemia and lipidaemia. The molecular structure of curcumins allows to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models. The aim of our study performed a systematic review and meta-analysis to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated type 2 diabetes. The papers included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for different sources of variation among studies. Cohen’s d, with 95% confidence interval (CI) was used as a measure of the effect size. Heterogeneity was assessed while using Q statistics. The ANOVA-Q test was used to value the differences among groups. Publication bias was analyzed and represented by a funnel plot. Curcumin treatment does not show a statistically significant reduction between treated and untreated patients. On the other hand, glycosylated hemoglobin, homeostasis model assessment (HOMA), and low-density lipoprotein (LDL) showed a statistically significant reduction in subjects that were treated with curcumin, respectively (p = 0.008, p < 0.001, p = 0.021). When considering HBA1c, the meta-regressions only showed statistical significance for gender (p = 0.034). Our meta-analysis seems to confirm the benefits on glucose metabolism, with results that appear to be more solid than those of lipid metabolism. However, further studies are needed in order to test the efficacy and safety of curcumin in uncomplicated type 2 diabetes.


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