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Cancers Sep 2021We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature... (Review)
Review
We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor () and vitamin D binding protein () genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61-4.56), although with large heterogeneity across studies (I = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the and genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation.
PubMed: 34638299
DOI: 10.3390/cancers13194815 -
Mediators of Inflammation 2018Inflammasomes are multiprotein complexes that can sense pathogen-associated molecular patterns and damage-associated molecular signals. They are involved in the... (Review)
Review
Inflammasomes are multiprotein complexes that can sense pathogen-associated molecular patterns and damage-associated molecular signals. They are involved in the initiation and development of inflammation via activation of IL-1 and IL-18. Many recent studies suggest a strong correlation between inflammasomes and neurological diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD). Several components of inflammasomes, such as nucleotide-binding oligomerization domain- (NOD-) like receptor, absent in melanoma 2- (AIM2-) like receptors (ALRs), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1, as well as the upstream factors and downstream effectors, are associated with the initiation and development of MS and its animal model, experimental autoimmune encephalomyelitis. Additionally, inflammasomes affect the efficacy of interferon- therapy in patients with MS. Finally, the strong association of inflammasomes with AD and PD needs to be further studied. In this review of latest literatures, we comprehensively tease out diverse roles of different kinds of inflammasomes in neuroimmune and neurodegenerative diseases, especially in the perspective of double roles involved in pathogenesis, and identify future research priorities.
Topics: Alzheimer Disease; Animals; Humans; Inflammasomes; Multiple Sclerosis; Neurodegenerative Diseases; Parkinson Disease
PubMed: 29849483
DOI: 10.1155/2018/1549549 -
International Journal of Molecular... Dec 2022Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring... (Review)
Review
Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring proper bone growth and functioning, and its deficiencies are indicated in various diseases, mainly in the proper structure and function of the skeleton. In this review, we focus on the most important components of the vitamin D metabolic pathway, in correlation with selected orthopedic conditions. Records were obtained from the PubMed database in a timeline of 2010-2022. The keywords were as follows: vitamin D/cholesterol/vitamin D binding protein/ VDBP/Cytochrome/CYP24A1/CYP 27B1/Vitamin D receptor/VDR/ + diseases (ACL reconstruction, rotator cuff, arthroplasty knee/hip/shoulder). The recent original studies were analyzed, discussed, and the most important data were shown. The vast majority of articles concern the metabolite of vitamin D (25(OH)D), which is measured as a standard in diagnostic laboratories. Even though there is a lot of valuable information in the literature, we believe that the other elements of the vitamin D pathway also deserve attention and suggest their research in correlation with orthopedic disorders to supplement the missing knowledge on this topic.
Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Metabolic Networks and Pathways; Orthopedics; Receptors, Calcitriol; Vitamin D; Vitamin D3 24-Hydroxylase; Vitamins
PubMed: 36555202
DOI: 10.3390/ijms232415556 -
Psychiatria Polska Apr 2022Currently, we observe a huge number of publications describing the role of glycine transporter (GlyT1) inhibitors in schizophrenia treatment. The concept of application... (Review)
Review
Currently, we observe a huge number of publications describing the role of glycine transporter (GlyT1) inhibitors in schizophrenia treatment. The concept of application for these drugs derives from the glutamatergic theory of schizophrenia. This theory explains psychotic disturbances as the consequence of NMDA receptor functioning defect. The role of the mentioned receptor depends mostly on the presence of cofactors. One such cofactor is the simplest aminoacid, glycine. This amino acid affects the glycine-binding site, located on the NR1 subunit of NMDAR and enables activation of the receptor. Substances enhancing the access of glycine to the receptor could hypothetically improve neuroplasticity. Higher efficacy of these neuroplastic processes may protect from cognitive deterioration and negative symptoms in the course of schizophrenia. In this article we present a systematic review of current literature on the topic of GlyT1 inhibitors in schizophrenia treatment (the state of literature as of November 2019). Firstly, we described the preclinical reasons for glycine enhancement use. Next, we used CINAHL, EMBASE, EMCARE, Medline, PsycINFO, PubMed and Google Scholar databases to extract and analyze evidence from clinical trials. GlyT1 inhibitors seem to have a potential in searching for novel substances in the treatment of negative symptoms, but their capacity to reduce cognitive deficits is not evidenced. So far, the clinical efficacy of several substances was proven, including N-methylglycine (sarcosine), bitopertin and derivatives obtained with chemical synthesis. Some of these substances demonstrate a beneficial clinical effect, but the number of published reports in this area is disproportionate to the value of evidence.
Topics: Glycine; Glycine Plasma Membrane Transport Proteins; Humans; Receptors, N-Methyl-D-Aspartate; Sarcosine; Schizophrenia
PubMed: 35988070
DOI: 10.12740/PP/OnlineFirst/126661 -
PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
The Cochrane Database of Systematic... Aug 2012Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU-486) competitively binds and inhibits progesterone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU-486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials.
OBJECTIVES
To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre-menopausal women.
SEARCH METHODS
We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions.
SELECTION CRITERIA
Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre-menopausal women with confirmed uterine fibroids were included.
DATA COLLECTION AND ANALYSIS
Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta-analyses were performed using the fixed-effect model.
MAIN RESULTS
Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I(2) = 0%). Three studies (Bagaria 2009; Engman 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) -0.02; 95% CI -0.38 to 0.41; 99 women). Two studies (Bagaria 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) -77.24; 95% CI -240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I(2) = 0%). Only one study (Bagaria 2009) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study (Fiscella 2006) suggested significant improvements (P < 0.001) for specific quality of life outcomes.
AUTHORS' CONCLUSIONS
Mifepristone reduced heavy menstrual bleeding and improved fibroid-specific quality of life. However, it was not found to reduce fibroid volume. Further well-designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids.
Topics: Female; Humans; Leiomyoma; Menorrhagia; Mifepristone; Premenopause; Randomized Controlled Trials as Topic; Receptors, Progesterone; Tumor Burden; Uterine Neoplasms
PubMed: 22895965
DOI: 10.1002/14651858.CD007687.pub2 -
BMC Medical Genomics Sep 2019Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD).
METHODS
We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis.
RESULTS
We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms.
CONCLUSIONS
Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.
Topics: Disease Susceptibility; Humans; Lipopolysaccharide Receptors; Mannose-Binding Lectin; Odds Ratio; Phenotype; Pneumococcal Infections; Polymorphism, Genetic; RNA, Long Noncoding; Risk Factors
PubMed: 31519222
DOI: 10.1186/s12920-019-0572-x -
Arab Journal of Urology Mar 2018To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve... (Review)
Review
OBJECTIVES
To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve their fertility potential, as testosterone replacement therapy (TRT) inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age.
MATERIALS AND METHODS
We performed a comprehensive literature review for the years 1978-2017 via PubMed. Also abstracts from major urological/surgical conferences were reviewed. Review was consistent with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) criteria. We used Medical Subject Heading terms for the search including 'testosterone replacement therapy' or 'TRT' and 'male infertility'.
RESULTS
In all, 91 manuscripts were screened and the final number used for the review was 56. All studies included were performed in adults, were written in English and had an abstract available.
CONCLUSIONS
Exogenous testosterone inhibits spermatogenesis. Hypogonadal men wanting to preserve their fertility and at the same time benefiting from TRT effects can be prescribed selective oestrogen receptor modulators or testosterone plus low-dose human chorionic gonadotrophin (hCG). Patients treated for infertility with hypogonadotrophic hypogonadism can be prescribed hCG alone at first followed by or in combination from the start with follicle-stimulating hormone preparations.
PubMed: 29713545
DOI: 10.1016/j.aju.2017.11.011 -
Advances in Clinical and Experimental... Aug 2017The Notch signaling pathway has been associated with the regulation of self-renewal capacity, cell cycle exit, and survival. However, the relationship between the Notch... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Notch signaling pathway has been associated with the regulation of self-renewal capacity, cell cycle exit, and survival. However, the relationship between the Notch signaling pathway and HNSCC remains controversial.
OBJECTIVES
A meta-analysis was conducted to evaluate the role of Notch signaling pathway in HNSCC.
MATERIAL AND METHODS
Relevant studies published until March 31, 2015 were identified by searching the PubMed, EMBASE and Ovid database.
RESULTS
A total of 9 articles were eligible for this meta-analysis. The meta-analysis results showed that the expression of Notch1, Notch3 and NICD was significantly higher in HNSCC as compared with control tissue. There was no significant difference in Jagged1 and HES1 expression between HNSCC and control tissue. Stratified analysis results showed that the expression of Notch1 was significantly higher in poor differentiation, III and IV stage and positive lymph node metastasis patients. Additionally, over-expression of Notch1, NICD, HES1 and DLL4 significantly predicted poor OS in HNSCC patients.
CONCLUSION
The Notch signaling pathway plays an important role in tumor development of HNSCC. Inhibition of the Notch signaling pathway is a potential therapeutic method of HNSCC.
Topics: Adaptor Proteins, Signal Transducing; Calcium-Binding Proteins; Carcinoma, Squamous Cell; Cell Differentiation; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Neoplasm Staging; Odds Ratio; Receptor, Notch1; Receptors, Notch; Risk Factors; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Survival Analysis; Time Factors; Transcription Factor HES-1
PubMed: 29068587
DOI: 10.17219/acem/64000 -
Frontiers in Immunology 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and type I interferon plays an important role in its pathogenesis. Anifrolumab is a new strategy for... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and type I interferon plays an important role in its pathogenesis. Anifrolumab is a new strategy for the treatment of systemic lupus erythematosus. It could antagonize the activity of all type 1 interferons by binding with type I interferon receptor subunit 1. The aim of our study was to evaluate the safety of anifrolumab in patients with moderate to severe SLE (excluding patients with active severe lupus nephritis or central nervous system lupus).
METHODS
Four databases (Embase, Cochrane, PubMed, Web of Science) were systematically searched from inception until December 2021 for randomized controlled trials (RCTs) evaluating the safety of anifrolumab versus placebo in SLE patients. Then, the incidence of adverse events in each study was aggregated using meta-analysis.
RESULTS
A total of 1160 SLE patients from four RCTs were included in the analysis. Serious adverse events were less common in the anifrolumab group than in the placebo group (RR: 0.76, 95% CI: 0.59-0.98, p<0.03). The most common adverse events included upper respiratory tract infection (RR: 1.48, 95% CI: 1.13-1.94, P=0.004), nasopharyngitis (RR: 1.66, 95% CI: 1.25-2.20, P=0.0004), bronchitis (RR: 1.96, 95% CI: 1.32-2.92, P=0.0009), and herpes zoster (RR: 3.40, 95% CI: 1.90-6.07, P<0.0001).
CONCLUSION
Anifrolumab is considered a well-tolerated option for the treatment of SLE patients with good safety.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com, identifier 202230054.
Topics: Antibodies, Monoclonal, Humanized; Chronic Disease; Humans; Interferon Type I; Lupus Erythematosus, Systemic; Randomized Controlled Trials as Topic; Receptor, Interferon alpha-beta
PubMed: 36211347
DOI: 10.3389/fimmu.2022.996662