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Scientific Reports Jul 2016Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically... (Meta-Analysis)
Meta-Analysis Review
Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically searched PubMed, Web of Science, and Embase to identify relevant studies until December 2015 and conducted a standard meta-analysis. Based on the inclusion and exclusion criteria, a total of 12 studies, including 2051 patients, were eligible for further analysis. Results showed that high survivin expression in RCC was associated with poor OS (HR = 2.84, 95% CI 1.68-4.79), CSS (HR = 2.36, 95% CI 1.41-3.95), and PFS (HR = 2.20, 95% CI 1.58-3.08). Survivin expression was also correlated with TNM stage (RR = 2.75, 95% CI 2.21-3.44), pathological T stage (RR = 2.19, 95% CI 1.75-2.75), lymph node metastasis (RR = 2.28, 95% CI 1.61-3.25), distant metastasis (RR = 1.56, 95% CI 1.16-2.08), Fuhrman grade (RR = 2.81, 95% CI 2.29-3.45), tumor size (RR = 1.49, 95% CI 1.24-1.78). Our study suggested that survivin was a prognostic marker in RCC. High survivin expression was correlated with poor prognosis and more advanced clinicopathological features, and it could serve as a biomarker for disease management.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Disease-Free Survival; Humans; Immunohistochemistry; Inhibitor of Apoptosis Proteins; Kidney Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Survivin
PubMed: 27411378
DOI: 10.1038/srep29794 -
Hormone Research in Paediatrics 2023Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of cortisol, aldosterone, or both. The most common type is the 21-hydroxylase enzyme deficiency in approximately 95% of cases resulting from CYP21A2 gene mutations or deletions.
OBJECTIVES
This study aimed to systematically review the national differences in CAH incidence and analyze the pooled results to determine disparities and whether ethnicity can predispose people to develop CAH.
METHODS
PubMed, Scopus, and LILACS were used to achieve results until June 22, 2018. Study eligibility criteria included availability of full-text; English, Spanish, or Portuguese languages; incidence or number of new cases; and number of live births or sample population. Only the classic CAH type (salt-wasting and simple-virilizing) was considered, and no distinction was made between the enzyme deficiency types.
RESULTS
This study summarizes the findings of 58 studies and 31 countries (from 1969 to 2017), in which the overall CAH incidence was 1:9,498 (95% confidence interval: 1:9,089, 1:9,945). Countries from the Eastern Mediterranean and Southeast Asia revealed the highest CAH incidence. The lowest incidence was reported in countries of the Western Pacific of Asia. No remarkable difference was observed in the Hispanics/Latino and White groups. However, they manifested a higher incidence of CAH than people identified as Black or of African descent. Published studies on CAH incidence in the sub-Saharan African region and parts of Europe were insufficient.
CONCLUSIONS
This study highlights the at-risk population for CAH and regions that need monitoring for CAH. The highest CAH incidence could be attributed to higher consanguinity, less genetic diversity, or other genetic causes since CAH is an inherited genetic disorder. Cultural practices in some places regarding consanguineous unions or geographic isolation may directly affect the incidence. Newborn screening for CAH may be unavailable in many developing countries, thereby affecting the actual CAH incidence. Therefore, healthcare workers should be trained to recognize CAH at an early stage to reduce its complications and mortality.
Topics: Infant, Newborn; Humans; Adrenal Hyperplasia, Congenital; Neonatal Screening; Adrenal Cortex; Mutation; Steroid 21-Hydroxylase
PubMed: 35973409
DOI: 10.1159/000526401 -
Medicine Jun 2016The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix... (Meta-Analysis)
Meta-Analysis Review
Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case-control trials.
The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61-11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91-3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63-7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52-6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06-2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48-2.20, P = 0.95).The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.
Topics: Biomarkers, Tumor; Case-Control Studies; Clinical Trials as Topic; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Pituitary Neoplasms; Tissue Inhibitor of Metalloproteinase-2
PubMed: 27310993
DOI: 10.1097/MD.0000000000003904 -
BMC Genomics Aug 2022The histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including...
BACKGROUND
The histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including T-box riboswitches in Firmicutes and Actinobacteria and RNA attenuators in Proteobacteria. Using a comparative genomic approach, we previously identified a novel DNA-binding transcription factor (named HisR) that controls the histidine metabolism genes in diverse Gram-positive bacteria from the Firmicutes phylum.
RESULTS
Here we report the identification of HisR-binding sites within the regulatory regions of the histidine metabolism and transport genes in 395 genomes representing the Bacilli, Clostridia, Negativicutes, and Tissierellia classes of Firmicutes, as well as in 97 other HisR-encoding genomes from the Actinobacteria, Proteobacteria, and Synergistetes phyla. HisR belongs to the TrpR family of transcription factors, and their predicted DNA binding motifs have a similar 20-bp palindromic structure but distinct lineage-specific consensus sequences. The predicted HisR-binding motif was validated in vitro using DNA binding assays with purified protein from the human gut bacterium Ruminococcus gnavus. To fill a knowledge gap in the regulation of histidine metabolism genes in Firmicutes genomes that lack a hisR repressor gene, we systematically searched their upstream regions for potential RNA regulatory elements. As result, we identified 158 T-box riboswitches preceding the histidine biosynthesis and/or transport genes in 129 Firmicutes genomes. Finally, novel candidate RNA attenuators were identified upstream of the histidine biosynthesis operons in six species from the Bacillus cereus group, as well as in five Eubacteriales and six Erysipelotrichales species.
CONCLUSIONS
The obtained distribution of the HisR transcription factor and two RNA-mediated regulatory mechanisms for histidine metabolism genes across over 600 species of Firmicutes is discussed from functional and evolutionary points of view.
Topics: Actinobacteria; Bacteria; DNA; Gene Expression Regulation, Bacterial; Gram-Positive Bacteria; Histidine; Humans; Phylogeny; Riboswitch; Transcription Factors
PubMed: 36008760
DOI: 10.1186/s12864-022-08796-y -
Urology Journal Jul 2015Prostate cancer (PCa) is one of the most commonly diagnosed male malignancies. Numerous studies have investigated the role of genetic variants in PCa risk. However,... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Prostate cancer (PCa) is one of the most commonly diagnosed male malignancies. Numerous studies have investigated the role of genetic variants in PCa risk. However, the results remain unclear. The purpose of this study was to evaluate the relationship between single-nucleotide polymorphism (SNP) rs2228001 in xeroderma pigmentosum group C (XPC), SNP rs4073 in interleukin 8 (IL8), and SNP rs2279744 in mouse double minute 2 (MDM2) homolog gene with PCa susceptibility.
MATERIALS AND METHODS
Electronic database of PubMed, Medline, and Embase were searched for eligible articles published between January 2000 and April 2014. The odd ratio (OR) with its 95% confidence interval (CI) were calculated to estimate the strength of association.
RESULTS
A total 18 case-control studies, including 5725 PCa cases and 5900 healthy controls, were screened out. Six studies were eligible for each SNP. For XPC 939A/C polymorphism, no significant association was found with PCa risk in the whole population (P > .05). No relationship in subgroup analysis was found by ethnicity. For IL8 -251T/A variant, the A allele was not related with PCa risk in any genetic models when compared with those individuals without A allele. For MDM2 -309T/G mutation, the G allele was not associated with the increased risk of PCa in total population and subgroup analysis by ethnicity as well.
CONCLUSION
Our study demonstrated that all these three genetic polymorphisms were not associated with an increased risk of developing PCa, which might also provide an insight into the future research. Further large-scale studies with concerning the gene-gene and gene-environment interactions are needed to elucidate final conclusion.
Topics: Animals; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Male; Prostatic Neoplasms; Risk Factors; Xeroderma Pigmentosum Group D Protein
PubMed: 26135929
DOI: No ID Found -
British Medical Bulletin 2015Mitochondrial diseases are a group of heterogeneous disorders for which no curative therapy is currently available. Several drugs are currently being pursued as... (Review)
Review
INTRODUCTION
Mitochondrial diseases are a group of heterogeneous disorders for which no curative therapy is currently available. Several drugs are currently being pursued as candidates to correct the underlying biochemistry that causes mitochondrial dysfunction.
SOURCES OF DATA
A systematic review of pharmacological therapeutics tested using in vitro, in vivo models and clinical trials. Results presented from database searches undertaken to ascertain compounds currently being pioneered to treat mitochondrial disease.
AREAS OF AGREEMENT
Previous clinical research has been hindered by poorly designed trials that have shown some evidence in enhancing mitochondrial function but without significant results.
AREAS OF CONTROVERSY
Several compounds under investigation display poor pharmacokinetic profiles or numerous off target effects.
GROWING POINTS
Drug development teams should continue to screen existing and novel compound libraries for therapeutics that can enhance mitochondrial function. Therapies for mitochondrial disorders could hold potential cures for a myriad of other ailments associated with mitochondrial dysfunction such as neurodegenerative diseases.
Topics: Animals; Electron Transport; Homeostasis; Humans; Mitochondria; Mitochondrial Diseases; Molecular Targeted Therapy; Neurodegenerative Diseases; Organelle Biogenesis; Organelles; Unfolded Protein Response
PubMed: 26590387
DOI: 10.1093/bmb/ldv046 -
Cytokine Feb 2021Zinc (Zn) is a trace metal that is considered to have an impact on chronic inflammation. However, findings of clinical trials have been inconsistent. The present... (Meta-Analysis)
Meta-Analysis
Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Zinc (Zn) is a trace metal that is considered to have an impact on chronic inflammation. However, findings of clinical trials have been inconsistent. The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence on the effectiveness of Zn supplements on markers of inflammation and oxidative stress.
METHODS
A systematic search in PubMed, Scopus, Web of Science and Cochrane Library was undertaken to identify relevant randomized controlled trials (RCTs) assessing the impact of Zn on inflammation and oxidative stress until 17 August 2020. We applied a random-effects method to obtain effect sizes (ES) and 95% confidence intervals (CIs). Meta-regression was used to detect the potential source of between-study heterogeneity.
RESULTS
Twenty-one eligible RCTs comprising 1321 participants were included in the meta-analysis. In comparison with the control groups, serum C-reactive protein (CRP) (ES = -0.92 mg/L, 95% CI = [-1.36, -0.48], P < 0.001, I = 90.2%), tumor necrosis factor-alpha (TNF-α) (ES = -0.49 pg/mL, 95% CI = [-084, -0.14], P = 0.006, I = 34.6%) and malondialdehyde (MDA) (ES = -0.42, 95% CI = [-083, -0.01], P = 0.04, I = 76.1%) were significantly reduced in the groups receiving Zn. Serum interleukin 6 (ES = -1.02 pg/mL, 95% CI = [-2.06, 0.02], P = 0.05, I = 92.3%) was marginally reduced following Zn supplementation. Moreover, treatment duration was found as the source of inter-study heterogeneity.
CONCLUSION
This meta-analysis suggests that Zn supplements reduce serum concentrations of markers of inflammation and oxidation: CRP, TNF-α and MDA.
Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Dietary Supplements; Humans; Inflammation; Malondialdehyde; Middle Aged; Oxidative Stress; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Young Adult; Zinc
PubMed: 33333394
DOI: 10.1016/j.cyto.2020.155396 -
Journal of Diabetes Research 2020The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have unique immunomodulatory capacities and have been considered as a promising interventional strategy for T1DM. Stem cell therapy in T1DM has been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to update the efficacy and safety of stem cell therapy in patients with T1DM.
METHODS
We systematically searched the Medline, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Wan Fang Data, China National Knowledge Infrastructure, VIP database, and the Chinese Biomedical Literature Database (SinoMed) for relevant studies published before March 19, 2019. The outcomes included parameters for glycemic control (i.e., glycosylated hemoglobin (HbA1c) levels and insulin dosages), cell function (i.e., fasting C-peptide levels and area-under-curve of C-peptide concentration (AUCC)), and relative risk of adverse events. Statistical analysis was conducted by using RevMan 5.3 and Stata 12.0.
RESULTS
Five randomized controlled trials (RCTs) and eight nonrandomized concurrent control trials (NRCCTs) with a total of 396 individuals were finally included into the meta-analysis. Among RCTs, stem cell therapy could significantly reduce HbA1c levels (MD = -1.20, 95% CI -1.91 to -0.49, = 0.0009) and increase fasting C-peptide levels (MD = 0.25, 95% CI 0.04 to 0.45, = 0.02) and AUCC (SMD = 0.66, 95% CI 0.13 to 1.18, = 0.01). Stem cell therapy could also reduce insulin dosages (SMD = -2.65, 95% CI -4.86 to -0.45, = 0.02) at 6 months after treatment. NRCCTs also had consistent results. Furthermore, RCTs showed stem cell therapy did not increase relative risk of gastrointestinal symptom (RR = 0.69, 95% CI 0.14 to 3.28, = 0.64) and infection (RR = 0.97, 95% CI 0.40 to 2.34, = 0.95). However, NRCCTs showed stem cell therapy increased relative risk of gastrointestinal symptom (RR = 44.49, 95% CI 9.20 to 215.18, < 0.00001).
CONCLUSION
Stem cell therapy for T1DM may improve glycemic control and cell function without increasing the risk of serious adverse events. Stem cell therapy may also have a short-term (3-6 months) effect on reducing insulin dosages.
Topics: Area Under Curve; C-Peptide; Diabetes Mellitus, Type 1; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Risk; Stem Cell Transplantation; Treatment Outcome
PubMed: 33102605
DOI: 10.1155/2020/5740923 -
Epigenetics Sep 2022Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a...
Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 region of the gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 . Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 region of the gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.
Topics: DNA Methylation; Exons; Female; Humans; Infant; Infant, Newborn; Pregnancy; Protein Processing, Post-Translational; Receptors, Glucocorticoid
PubMed: 34519616
DOI: 10.1080/15592294.2021.1980691 -
Cancer Epidemiology, Biomarkers &... Aug 2014Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations... (Meta-Analysis)
Meta-Analysis Review
Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and human epidermal growth factor receptor type 2 (HER2) overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI), and/or [(18)F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 articles, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on five or more studies and robustness in subgroup analyses were as follows: the presence of microcalcifications on mammography [pooled odds ratio (pOR), 3.14; 95% confidence interval (CI), 2.46-4.00] or ultrasound (mass-associated pOR, 2.95; 95% CI, 2.34-3.71), branching or fine linear microcalcifications (pOR, 2.11; 95% CI, 1.07-4.14) or extremely dense breasts on mammography (pOR, 1.37; 95% CI, 1.07-1.76), and washout (pOR, 1.57; 95% CI, 1.11-2.21) or fast initial kinetics (pOR, 2.60; 95% CI, 1.43-4.73) on MRI all increased the chance of HER2 overexpression. Maximum [(18)F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference, +0.76; 95% CI, 0.10-1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up.
Topics: Breast Neoplasms; Diagnostic Imaging; Female; Humans; Phenotype; Receptor, ErbB-2
PubMed: 24807204
DOI: 10.1158/1055-9965.EPI-13-1170