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Endocrinology, Diabetes & Metabolism Jan 2022Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. Chemerin, a novel adipokine, is involved in inflammation,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. Chemerin, a novel adipokine, is involved in inflammation, energy metabolism, adipogenesis, angiogenesis and insulin secretion in the adipose cells and ovary. This systematic review with meta-analysis aimed to compare serum and follicular fluid (FF) chemerin and ovarian chemerin mRNA expression among women with PCOS and non-PCOS.
METHODS
Electronic databases including Web of Science, PubMed, Google Scholar, Scopus, Cochrane and CINAHL were used for a comprehensive search through April 2021. Of the 174 articles initially identified, 22 studies met the eligibility criteria. A random-effects model with a weighted mean difference (WMD) and 95% confidence interval (CI) was performed to compare the outcomes between groups. Subgroup and sensitivity analyses were performed to detect the sources of heterogeneity.
RESULTS
Women with PCOS compared to without PCOS showed significantly higher serum chemerin [WMD: 12.02 pg/ml (95% CI: [10.92, 13.13]), p < .001], chemerin mRNA expression [WMD: 0.38% (95% CI [0.25, 0.52]), p = .001] and FF chemerin [(WMD): 41.7 pg/ml (95% CI [17.89, 65.5]) p < .001]. Further, serum chemerin remained high in PCOS women even with subgroup analysis based on body mass index (BMI) or sample size (p < .001). Serum chemerin was higher in women with PCOS and higher BMI [(WMD): 3.29 pg/ml (95% CI: [2.73, 3.384]), p < .001]. The expression of chemerin mRNA was significantly higher in the PCOS group compared to the control group [WMD: 0.38% (95% CI [0.25, 0.52]), p < .001].
CONCLUSION
Serum and FF chemerin and mRNA expression were higher in the PCOS group compared to the controls. Further, serum chemerin was higher in PCOS women with higher BMI compared to lower BMI. The present findings illustrate that chemerin may be associated with PCOS status and BMI, independently.
Topics: Adipokines; Chemokines; Female; Follicular Fluid; Humans; Polycystic Ovary Syndrome; RNA, Messenger
PubMed: 34699139
DOI: 10.1002/edm2.307 -
Reviews in Medical Virology Jan 2024The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity,... (Review)
Review
The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID-19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real-world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID-19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID-19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID-19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID-19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.
Topics: Humans; COVID-19; COVID-19 Vaccines; mRNA Vaccines; SARS-CoV-2; Treatment Outcome
PubMed: 38282403
DOI: 10.1002/rmv.2515 -
Neuromodulation : Journal of the... Jan 2023Spinal cord stimulation (SCS) is a last-resort treatment for patients with chronic neuropathic pain. The mechanism underlying SCS and pain relief is not yet fully... (Review)
Review
OBJECTIVES
Spinal cord stimulation (SCS) is a last-resort treatment for patients with chronic neuropathic pain. The mechanism underlying SCS and pain relief is not yet fully understood. Because the inflammatory balance between pro- and anti-inflammatory molecules in the spinal nociceptive network is pivotal in the development and maintenance of neuropathic pain, the working mechanism of SCS is suggested to be related to the modulation of this balance. The aim of this systematic review is to summarize and understand the effects of different SCS paradigms on the central inflammatory balance in the spinal cord.
MATERIALS AND METHODS
A systematic literature search was conducted using MEDLINE, Embase, and PubMed. All articles studying the effects of SCS on inflammatory or glial markers in neuropathic pain models were included. A quality assessment was performed on predetermined entities of bias.
RESULTS
A total of 11 articles were eligible for this systematic review. In general, induction of neuropathic pain in rats results in a proinflammatory state and at the same time an increased activity/expression of microglial and astroglial cells in the spinal cord dorsal horn. Conventional SCS seems to further enhance this proinflammatory state and increase the messenger RNA expression of microglial markers, but it also results in a decrease in microglial protein marker levels. High-frequency and especially differential targeted multiplexed SCS can not only restore the balance between pro- and anti-inflammatory molecules but also minimize the overexpression/activation of glial cells. Quality assessment and risk of bias analysis of the studies included make it clear that the results of these preclinical studies must be interpreted with caution.
CONCLUSIONS
In summary, the preclinical findings tend to indicate that there is a distinct SCS paradigm-related effect in the modulation of the central inflammatory balance of the spinal dorsal horn.
Topics: Rats; Animals; Spinal Cord Stimulation; Neuralgia; Pain Management; Spinal Cord; Spinal Cord Dorsal Horn
PubMed: 35931643
DOI: 10.1016/j.neurom.2022.04.049 -
International Journal of Molecular... Oct 2022The CTNNB1 Syndrome is a rare neurodevelopmental disorder associated with developmental delay, intellectual disability, and delayed or absent speech. The aim of the... (Review)
Review
The CTNNB1 Syndrome is a rare neurodevelopmental disorder associated with developmental delay, intellectual disability, and delayed or absent speech. The aim of the present study is to systematically review the available data on the prevalence of clinical manifestations and to evaluate the correlation between phenotype and genotype in published cases of patients with CTNNB1 Syndrome. Studies were identified by systematic searches of four major databases. Information was collected on patients' genetic mutations, prenatal and neonatal problems, head circumference, muscle tone, EEG and MRI results, dysmorphic features, eye abnormalities, early development, language and comprehension, behavioral characteristics, and additional clinical problems. In addition, the mutations were classified into five groups according to the severity of symptoms. The study showed wide genotypic and phenotypic variability in patients with CTNNB1 Syndrome. The most common moderate-severe phenotype manifested in facial dysmorphisms, microcephaly, various motor disabilities, language and cognitive impairments, and behavioral abnormalities (e.g., autistic-like or aggressive behavior). Nonsense and missense mutations occurring in exons 14 and 15 were classified in the normal clinical outcome category/group because they had presented an otherwise normal phenotype, except for eye abnormalities. A milder phenotype was also observed with missense and nonsense mutations in exon 13. The autosomal dominant CTNNB1 Syndrome encompasses a wide spectrum of clinical features, ranging from normal to severe. While mutations cannot be more generally categorized by location, it is generally observed that the C-terminal protein region (exons 13, 14, 15) correlates with a milder phenotype.
Topics: Pregnancy; Female; Humans; Codon, Nonsense; Phenotype; Intellectual Disability; Syndrome; Genotype; Mutation; Eye Abnormalities; beta Catenin
PubMed: 36293418
DOI: 10.3390/ijms232012564 -
Annals of Coloproctology Apr 2023Intestinal fibrosis is a common complication of inflammatory bowel diseases. However, the possible involvement of epithelial-mesenchymal transition (EMT) has been... (Review)
Review
PURPOSE
Intestinal fibrosis is a common complication of inflammatory bowel diseases. However, the possible involvement of epithelial-mesenchymal transition (EMT) has been scarcely investigated. This systematic review aims to search through research papers that are focusing on messenger RNA (mRNA) and protein expression profile in EMT in fistula or in intestinal fibrosis.
METHODS
Electronic exploration was performed until April 24, 2019 through PubMed, Ovid, Science Direct, and Scopus databases with the terms of "fistula" OR "intestinal fibrosis" AND "epithelial-mesenchymal transition". Two independent reviewers scrutinized the suitability of the title and abstract before examining the full text that met the inclusion criteria. For each study, the sample types that were used, methods for analysis, and genes expressed were identified. The list of genes was further analyzed using DAVID (Database for Annotation, Visualization, and Integrated Discovery) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway.
RESULTS
There were 896 citations found; however, only 3 studies fulfilled the requirements. Among the EMT-related genes, 5 were upregulated genes at mRNA level while 6 were at protein level. However, only 2 downregulated genes were found at each mRNA and protein level. Of the 4 inflammation-related genes found, 3 genes were upregulated at mRNA level and 1 at protein level. These genes were confirmed to be involved in the development of inflammatory induced fibrosis and fistula through EMT. Results from quantitative real-time polymerase chain reaction analysis were consistent with the process of EMT, confirmed by the western blot protein analysis.
CONCLUSION
Many significant genes which are involved in the process of EMT in fistula and intestinal fibrosis have been identified. With high-end technology many more genes could be identified. These genes will be good molecular targets in the development of biomarkers for precision drug targeting in the future treatment of intestinal fibrosis and fistula.
PubMed: 34856655
DOI: 10.3393/ac.2021.00584.0083 -
Molecular Psychiatry Mar 2022The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and... (Meta-Analysis)
Meta-Analysis
The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.
Topics: Bipolar Disorder; Brain; Depressive Disorder, Major; Disks Large Homolog 4 Protein; Humans; Mood Disorders; RNA, Messenger
PubMed: 35022529
DOI: 10.1038/s41380-021-01410-9 -
JAMA Pediatrics Jan 2023Published data on COVID-19 mRNA vaccine-associated myopericarditis in adolescents and young adults have been derived from small case series, national population-based... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Published data on COVID-19 mRNA vaccine-associated myopericarditis in adolescents and young adults have been derived from small case series, national population-based studies, or passive reporting systems. Pooled evidence from a larger, international cohort is scarce.
OBJECTIVE
To investigate the clinical features and early outcomes associated with myopericarditis after COVID-19 mRNA vaccination in a heterogeneous population of adolescents and young adults.
DATA SOURCES
PubMed and EMBASE were searched through August 2022. Language restrictions were not applied.
STUDY SELECTION
Observational studies and case series describing COVID-19 vaccine-associated myopericarditis in adolescents and young adults aged 12 to 20 years and reporting clinical characteristics and early outcomes were included.
DATA EXTRACTION AND SYNTHESIS
Two independent investigators extracted relevant data from each study. One-group meta-analysis in a random effects model was performed. The Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed.
MAIN OUTCOMES AND MEASURES
The primary outcomes were clinical features and early outcomes for COVID-19 mRNA vaccine-associated myopericarditis, including incident rate, cardiac findings, hospitalization, intensive care unit (ICU) admission, and in-hospital mortality.
RESULTS
A total of 23 observational studies were identified, including 854 individuals (mean age, 15.9 [95% CI, 15.5-16.2] years) with COVID-19 vaccine-associated myopericarditis. Male sex was predominant, at 90.3% (95% CI, 87.3%-93.2%) of individuals. The incident rate was higher after the second dose than the first dose, with 74.4% (95% CI, 58.2%-90.5%) of events occurring after the second dose. Most patients (84.4% [95% CI, 80.5%-88.3%] of patients) had preserved left ventricular (LV) function. Of the 15.6% (95% CI, 11.7%-19.5%) of patients with LV systolic dysfunction (LV ejection fraction [LVEF] <55%), most (14.1% [95% CI, 10.2%-18.1%]) were mild (ie, LVEF 45%-54%), and only 1.3% (95% CI, 0%-2.6%) of patients had severe LV systolic dysfunction (ie, LVEF<35%). Interestingly, cardiac magnetic resonance imaging revealed late gadolinium enhancement in 87.2% (95% CI, 79.8%-94.7%) of patients. Although 92.6% (95% CI, 87.8%-97.3%) of patients were hospitalized and 23.2% (95% CI, 11.7%-34.7%) of patients required ICU admission, inotropes were used in only 1.3% (95% CI, 0%-2.7%) of patients, no patients died or required mechanical support, and the hospital length of stay was 2.8 (95% CI, 2.1-3.5) days.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found low incidence rate and largely favorable early outcomes of COVID-19 mRNA vaccine-associated myopericarditis in adolescents and young adults from a wide range of populations. These findings are reassuring but continued follow-up is warranted.
Topics: Humans; Male; Adolescent; Young Adult; COVID-19 Vaccines; COVID-19; Contrast Media; Gadolinium; Ventricular Dysfunction, Left; Vaccination; RNA, Messenger
PubMed: 36469338
DOI: 10.1001/jamapediatrics.2022.4768 -
International Journal of Molecular... Feb 2023Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and... (Review)
Review
Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and weakness, and multisystemic dysfunctions. This disorder is caused by an abnormal expansion of the CTG triplet at the gene that, when transcribed to expanded mRNA, can lead to RNA toxic gain of function, alternative splicing impairments, and dysfunction of different signaling pathways, many regulated by protein phosphorylation. In order to deeply characterize the protein phosphorylation alterations in DM1, a systematic review was conducted through PubMed and Web of Science databases. From a total of 962 articles screened, 41 were included for qualitative analysis, where we retrieved information about total and phosphorylated levels of protein kinases, protein phosphatases, and phosphoproteins in DM1 human samples and animal and cell models. Twenty-nine kinases, 3 phosphatases, and 17 phosphoproteins were reported altered in DM1. Signaling pathways that regulate cell functions such as glucose metabolism, cell cycle, myogenesis, and apoptosis were impaired, as seen by significant alterations to pathways such as AKT/mTOR, MEK/ERK, PKC/CUGBP1, AMPK, and others in DM1 samples. This explains the complexity of DM1 and its different manifestations and symptoms, such as increased insulin resistance and cancer risk. Further studies can be done to complement and explore in detail specific pathways and how their regulation is altered in DM1, to find what key phosphorylation alterations are responsible for these manifestations, and ultimately to find therapeutic targets for future treatments.
Topics: Animals; Adult; Humans; Myotonic Dystrophy; Phosphorylation; Alternative Splicing; RNA, Messenger; Muscular Atrophy; Muscle, Skeletal
PubMed: 36834509
DOI: 10.3390/ijms24043091 -
BMC Medicine Oct 2022Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.
METHODS
We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T cell responses, and safety profiles between fractional and standard dose groups.
RESULTS
We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2-specific nAbs and T cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose.
CONCLUSIONS
Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations.
Topics: Humans; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Protein Subunits; RNA, Messenger; SARS-CoV-2; Viral Vaccines
PubMed: 36284331
DOI: 10.1186/s12916-022-02600-0 -
Animal Genetics Jun 2023The FecB mutation in the sheep BMPRIB is strongly correlated with high ovulation traits but its mechanism remains unclear. This study explored differentially expressed... (Meta-Analysis)
Meta-Analysis Review
The FecB mutation in the sheep BMPRIB is strongly correlated with high ovulation traits but its mechanism remains unclear. This study explored differentially expressed genes (DEGs) and their associated molecular mechanisms that may be involved in FecB mutation-induced high ovulation from the perspective of the hypothalamic-pituitary-gonadal (HPG) axis by conducting a systematic review and meta-analysis. The PubMed, EMBASE, CNKI, WanFang, and CBM databases were searched for eligible articles published before August 2022, focusing on mRNA sequencing of different tissues in the HPG axis in sheep with different FecB genotypes. A total of 6555 DEGs were identified from the analysis of six published articles and experimental results from our laboratory. The DEGs were screened by vote-counting rank and robust rank aggregation. Among these, in the follicular phase, FKBP5, CDCA7 and CRABP1 were upregulated in the hypothalamus. INSM2 was upregulated, while LDB3 was downregulated in the pituitary. CLU, SERPINA14, PENK, INHA and STAR were upregulated, while FERMT2 and NPY1R were downregulated in the ovary. On the HPG axis, TAC1 was upregulated and NPNT was downregulated. Many DEGs were found in sheep with different FecB genotypes. The genes FKBP5, CDCA7, CRABP1, INSM2, LDB3, CLU, SERPINA14, PENK, INHA, STAR, FERMT2, NPY1R, TAC1 and NPNT, may be associated with FecB mutation-induced high ovulation in different tissues. These candidate genes will further improve the mechanism of multiple fertility traits induced by the FecB mutation from the perspective of the HPG axis.
Topics: Female; Sheep; Animals; RNA, Messenger; Genotype; Fertility; Ovulation; Phenotype
PubMed: 36811249
DOI: 10.1111/age.13304