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Sexual Medicine Apr 2023Erectile dysfunction (ED) is a common disease among elderly men, and novel therapy methods are needed for drug-refractory ED. As an extracellular vesicle, stem...
INTRODUCTION
Erectile dysfunction (ED) is a common disease among elderly men, and novel therapy methods are needed for drug-refractory ED. As an extracellular vesicle, stem cell-derived exosomes displayed erectile function improvement in rat ED models in some preclinical studies. However, the therapeutic efficacy has not been comprehensively evaluated.
AIM
To study the therapeutic effects of stem cell-derived exosomes on ED in preclinical studies and to investigate the potential mechanisms responsible for the efficacy.
METHODS
The systematic literature search was conducted in Web of Science, PubMed, and Embase to retrieve studies utilizing stem cell-derived exosomes for ED treatment. We extracted data of intracavernous pressure/mean artery pressure (ICP/MAP), and cavernosum structural changes in rat ED models before and after stem cell-derived exosome therapy. RevMan 5.3 was used to perform meta-analyses of ICP/MAP and cavernosum microstructural changes. Publication bias was assessed with the Egger test and funnel plot by Stata 15.0 (StataCorp).
MAIN OUTCOME MEASURES
Outcomes included ICP/MAP, smooth muscle, and endothelial markers-such as the ratio of smooth muscle to collagen and the expression of α-SMA (alpha smooth muscle actin), CD31 (cluster of differentiation 31), nNOS and eNOS (neuronal and endothelial nitric oxide synthase), TGF-β1 (transforming growth factor β1), and caspase 3 protein-to evaluate erectile function and microstructural changes. Forest plots of effect sizes were performed.
RESULTS
Of 146 studies retrieved, 11 studies were eligible. Pooled analysis showed that stem cell-derived exosomes ameliorated damaged ICP/MAP (standardized mean difference, 3.68; 95% CI, 2.64-4.72; < .001) and structural changes, including the ratio of smooth muscle to collagen and the expression of α-SMA, CD31, nNOS, eNOS, TGF-β1, and caspase 3 protein. Subgroup analysis indicated that exosome type and ED model type made no difference to curative effects.
CONCLUSION
This meta-analysis suggests the therapeutic efficacy of stem cell-derived exosomes for ED. Exosomes may restore erectile function by optimizing cavernosum microstructures.
PubMed: 36910707
DOI: 10.1093/sexmed/qfac019 -
BMJ Open Jun 2024The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC.
DESIGN
The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
DATA SOURCES
Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023.
STATISTICAL METHODS
Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs.
RESULTS
11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location.
CONCLUSIONS
In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.
Topics: Humans; Ki-67 Antigen; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Prognosis; Biomarkers, Tumor; Disease-Free Survival
PubMed: 38839387
DOI: 10.1136/bmjopen-2023-083637 -
Journal of Cancer Research and Clinical... Apr 2020MicroRNAs (miRNAs) participate in a variety of biological processes, including tumorigenesis, progression, invasion, and drug resistance to multiple cancers. Phosphatase...
PURPOSE
MicroRNAs (miRNAs) participate in a variety of biological processes, including tumorigenesis, progression, invasion, and drug resistance to multiple cancers. Phosphatase and tensin homolog (PTEN) is a cancer suppressor gene that has been certified to be regulated by miRNAs in various tumors, including colorectal cancer (CRC). In this review, we screened articles focusing on low PTEN expression in CRC, observed the expression of related miRNAs, analyzed their correlation and relationship with clinicopathological features, and discussed the possibility of these miRNAs as prognostic molecules.
METHODS
We conducted a systematic search for articles published in the Web of Science, PubMed and EBSCO databases between January 1, 2002, and July 18, 2019. We identified these studies by using combinations of the following index entries and key words: 'colorectal tumor OR colorectal neoplasm OR colorectal carcinoma OR colorectal cancer OR CRC', 'protein tyrosine phosphatase OR PTEN', and 'microRNA OR MiRNA OR miRNA OR MicroRNA'. Moreover, we evaluated the underlying association between alterations in PTEN and CRC prognosis.
RESULTS
PTEN expression was obviously lower in CRC tissues than in normal mucosa. However, PTEN expression did not differ significantly between adenoma and normal tissues. PTEN tends to be negatively associated with tumor size and metastasis. MiR-21, miR-200a, miR-543, miR-32, miR-92a, miR-26a, miR-106a and miR-181a were correlated with the downregulation of PTEN. MiR-26a, miR-106a and miR-181a were obviously higher in CRC tissues than in normal tissues, while PTEN was downregulated in CRC tissues. Additionally, miRNAs were mainly positively correlated with distant metastasis, followed by TNM stage. The relationship between miRNAs and tumor differentiation is controversial. However, there were no significant differences between miRNAs and either sex or age.
CONCLUSIONS
The loss of PTEN may be a diagnostic factor for CRC patients. The above-mentioned miRNAs may function as oncogenes in CRC and represent potential targets for CRC therapy. However, further prospective clinical studies are necessary.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Humans; MicroRNAs; PTEN Phosphohydrolase
PubMed: 32146564
DOI: 10.1007/s00432-020-03172-3 -
The Ocular Surface Oct 2019Numerous studies have reported a wide range of corneal epithelial dendritic cells (CEDC) density using in-vivo confocal microscopy in healthy participants. It is... (Meta-Analysis)
Meta-Analysis
PURPOSE
Numerous studies have reported a wide range of corneal epithelial dendritic cells (CEDC) density using in-vivo confocal microscopy in healthy participants. It is necessary to establish normal CEDC values for healthy corneas to enable differentiation from pathological corneas. This meta-analysis aimed to establish CEDC density and distribution and examine their relationship with age and sex.
METHODS
A systematic review of the literature of studies using the Heidelberg Retinal Tomograph with Rostock Corneal Module and reporting CEDC density in healthy subjects up to December 2018 was conducted via Medline, Google Scholar, Scopus, PubMed, Embase and Cochrane library. A random effect modeling approach was used to obtain the results of meta-analysis and meta-regression was conducted to estimate the effect of age and sex.
RESULTS
38 studies reported central and 9 reported peripheral inferior CEDC density of 1203 participants (mean age 46.0 ± 12.2, range 18-81 years). CEDC density in the central and peripheral inferior cornea was 26.4 ± 13.6 cells/mm (95% CI:22.5-26.8) and 74.9 ± 22.7 cells/mm (95%CI:59.8-90.0), respectively. No effect of age was found on central CEDC density (p = 0.63); whereas peripheral CEDC density decreased with increasing age (p = 0.02). CEDC density was not influenced by sex at either location (p > 0.48).
CONCLUSION
This study established that the density at the peripheral inferior cornea is three-fold higher than at the central cornea. Peripheral but not central CEDC density decreased with increasing age. There are limited studies in youth (<18 years), precluding a more detailed analysis. Sex does not appear to be a significant factor in CEDC density.
Topics: Cell Count; Cell Differentiation; Dendritic Cells; Epithelium, Corneal; Humans; Microscopy, Confocal; Reference Values
PubMed: 31279064
DOI: 10.1016/j.jtos.2019.07.001 -
Current Stem Cell Research & Therapy 2021Neurological diseases have different etiological causes. Contemporary, developing an effective treatment for these diseases is an ongoing challenge. Cell therapy is...
Evaluation of Differentiation Quality of Several Differentiation Inducers of Bone Marrow-derived Mesenchymal Stem Cells to Nerve Cells by Assessing Expression of Beta-tubulin 3 Marker: A Systematic Review.
Neurological diseases have different etiological causes. Contemporary, developing an effective treatment for these diseases is an ongoing challenge. Cell therapy is recognized as one of the promising solutions for the treatment of these diseases. Amongst various types of stem cells, bone marrow-derived mesenchymal stem cells (BM-MSC) are known to be the most widely used stem cells. These cells are endowed with appealing properties such as the ability to differentiate into other cell types, including the muscle, liver, glial, and nerve cells. In this review study, we have systematically evaluated the ability of a variety of chemical compounds used in the last ten years to differentiate BM-MSCs into neurons by examining the expression level of beta-tubulin 3 protein. The present study is a systematic search performed at three separate databases, including PubMed, ScienceDirect, and Embase from August 2009 to August 2019. The search results in the three mentioned databases were 323 articles and finally, 8 articles were selected and carefully examined considering the inclusion and exclusion criteria. The results showed that different chemical compounds such as ROCK inhibitors, sex steroid hormones, bFGF, NGF, Noggin, 4 OHT, TSA, VPA, Antidepressants, Neurosteroids (Dex and E2), and DHA are involved in different signaling pathways, such as ERK, AKT, BMP, DHA / GPR40, Rho-dependent phosphorylation, and histone deacetylase inhibitors. Further investigation of these signaling pathways may open the way for better differentiation of BM-MSCs into neurons.
Topics: Bone Marrow; Bone Marrow Cells; Cell Differentiation; Humans; Mesenchymal Stem Cells; Neurons; Tubulin
PubMed: 33655875
DOI: 10.2174/1574888X16666210303150814 -
Pathology, Research and Practice Dec 2019The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors.
METHOD
We searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters.
RESULTS
Sixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43-1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19-3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17-3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08-6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23-2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05).
CONCLUSIONS
High CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.
Topics: Biomarkers, Tumor; Female; Humans; Lymphatic Metastasis; Male; Microfilament Proteins; Middle Aged; Neoplasm Staging; Neoplasms; Nuclear Proteins; Risk Factors; Sex Factors; Signal Transduction
PubMed: 31685300
DOI: 10.1016/j.prp.2019.152683 -
The International Journal of Biological... Jun 2022FOXO3a (previously termed FKHRL1), plays an evolutionarily conserved role in the control of biological process, including DNA damage, apoptosis, and cell cycle... (Meta-Analysis)
Meta-Analysis
BACKGROUND
FOXO3a (previously termed FKHRL1), plays an evolutionarily conserved role in the control of biological process, including DNA damage, apoptosis, and cell cycle regulation. However, the role of FOXO3a in tumors remains controversial. This meta-analysis was conducted to evaluate the prognostic value of FOXO3a expression in patients with solid tumors.
METHODS
A systematic literature search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed. Eligible publications on FOXO3a and cancer prognosis were collected and screened according to the eligibility criteria. The combined odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were used to assess the prognostic value of FOXO3a. Stata 12.0 software was used for statistical analysis.
RESULTS
A total of 4058 patients from 21 articles on a variety of solid tumors were included. Meta-analysis showed that the increased FOXO3a expression level was associated with longer overall survival (HR = 0.62; 95% CI: 0.46-0.85). The pooled ORs indicated high expression level of FOXO3a in tumors was significantly associated with lymph node metastasis (OR = 0.46; 95% CI: 0.30-0.71), TNM stage (OR = 0.37; 95% CI: 0.25-0.54), tumor differentiation (OR = 0.46; 95% CI: 0.26-0.80), distant metastasis (OR = 0.44; 95% CI: 0.32-0.61), and age (OR = 1.28; 95% CI: 1.08-1.51). However, we did not observe a significant correlation between the high expression of FOXO3a and sex or tumor size.
CONCLUSIONS
The high expression level of FOXO3a was associated with better clinical outcomes in solid tumors. FOXO3a may therefore serve as a potential prognostic biomarker and a promising molecular target.
Topics: Biomarkers, Tumor; Humans; Lymphatic Metastasis; Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 35484793
DOI: 10.1177/03936155221095879 -
Medicine Jul 2020The high expression of long noncoding RNA ZEB1 anti-sense1 (ZEB1-AS1) has been reported in several types of cancer. However, most studies investigating this phenomenon... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The high expression of long noncoding RNA ZEB1 anti-sense1 (ZEB1-AS1) has been reported in several types of cancer. However, most studies investigating this phenomenon were either case reports or used small patient samples. The objective of this meta-analysis was to clarify the potential clinical values of ZEB1-AS1 in various cancers.
MATERIALS AND METHODS
The PubMed-MEDLINE, Web of Science, and EMBASE databases were searched, using systematic search terms, to find relevant research reports on this subject. The combined hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to explore the association between ZEB1-AS1 expression and overall survival (OS). The combined odd ratios (ORs) were calculated to evaluate the association between ZEB1-AS1 expression and pathological parameters. Data analysis was conducted in R software version 3.4.2. and Stata version 12.0 (College Station, TX: Stata Corp LP).
RESULTS
Ten studies including 963 cancer patients were selected as suitable for this study. The pooled hazards ratio (HR) indicated that high ZEB1-AS1 expression was strongly associated with poor OS (pooled HR = 2.26, 95% CI: 1.80-2.85, P < .0001) in the Chinese cancer patients. Also, a high expression of ZEB1-AS1 was related to metastasis (pooled HR = 3.38, 95% CI: 1.91-6.00, P < .0001), and advanced tumor stage (pooled HR = 0.48, 95% CI: 0.29-0.81, P = .005). The up-regulation of ZEB1-AS1 was not significantly associated with histological differentiation (P = .39), sex (P = .001), and age (P = .372) of cancer patients.
CONCLUSION
The high expression of ZEB1-AS1 significantly predicted poor OS, poor metastasis, and high tumor stage in cancer patients, demonstrating that high ZEB1-AS1 expression may serve as a biomarker of poor prognosis in the Chinese cancer patients.
Topics: Biomarkers, Tumor; Humans; Neoplasms; RNA, Long Noncoding
PubMed: 32756112
DOI: 10.1097/MD.0000000000021307 -
Frontiers in Oncology 2021Gallbladder carcinoma (GBC) is a rare gastrointestinal malignancy with poor prognosis. Adequate pre-treatment prediction of survival is essential for risk stratification...
BACKGROUND
Gallbladder carcinoma (GBC) is a rare gastrointestinal malignancy with poor prognosis. Adequate pre-treatment prediction of survival is essential for risk stratification and patient selection for aggressive surgery or adjuvant therapeutic strategy. Whole blood cell count (WBCC) derived indexes are broadly used as prognosticative biomarkers in various cancer types, but their utility in GBC needs to be validated.
METHODS
An extensive literature review was conducted in line with PRISMA guideline until June 31 2020, to identify original studies concerning WBCC-derived indexes as prognostic indicators in GBC. All relative parameters were extracted and pooled for statistical analyses.
RESULTS
Fourteen studies incorporating 2,324 patients were included with a high quality and low risk of biases. All 14 studies evaluated the prognostic value of NLR showing a significant correlation with OS in GBC patients (HR = 1.94, 0.001). Elevated NLR was revealed to correlate with TNM stage (stages III and IV, OR = 4.65, 0.001), tumor differentiation (OR = 2.37, 0.042), CA 19-9 (SMD = 0.47, = 0.01), but no significance was found with age, sex and CEA. Positive indicative value of MLR and PLR were also confirmed with a HR of 2.06 (0.001) and 1.34 (0.001), respectively.
CONCLUSION
The WBCC-derived indexes including NLR, MLR/LMR and PLR were validated to be useful prognostic parameters for predicting survival outcomes in GBC patients. These series of indexes, especially NLR, could improve risk stratification and facilitate better patient selection for surgical resection or aggressive chemotherapy in the decision making of GBC patients.
PubMed: 34262875
DOI: 10.3389/fonc.2021.707742 -
World Journal of Gastroenterology Feb 2021Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk factors for LNM have been controversial.
AIM
To evaluate risk factors for LNM in T1 ESCC.
METHODS
We searched Embase, PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC. Included studies were divided into LNM and non-LNM groups. We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features. Odds ratio (OR), mean differences and 95% confidence interval (CI) were assessed using a fixed-effects or random-effects model.
RESULTS
Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria. After excluding studies with heterogeneity based on influence analysis, tumor size (OR = 1.93, 95%CI = 1.49-2.50, < 0.001), tumor location (OR = 1.46, 95%CI = 1.17-1.82, < 0.001), macroscopic type (OR = 3.17, 95%CI = 2.33-4.31, < 0.001), T1 substage (OR = 6.28, 95%CI = 4.93-8.00, < 0.001), differentiation (OR = 2.11, 95%CI = 1.64-2.72, < 0.001) and lymphovascular invasion (OR = 5.86, 95%CI = 4.60-7.48, < 0.001) were found to be significantly associated with LNM. Conversely, sex, age and infiltrative growth pattern were not identified as risk factors for LNM.
CONCLUSION
A tumor size > 2 cm, lower location, nonflat macroscopic type, T1b stage, poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.
Topics: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Head and Neck Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Staging; Risk Factors
PubMed: 33716451
DOI: 10.3748/wjg.v27.i8.737