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European Journal of Clinical... Feb 2024Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells.... (Review)
Review
BACKGROUND
Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker.
AIMS
Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD.
METHODS
We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients.
RESULTS
A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation.
CONCLUSIONS
Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.
Topics: Adult; Humans; Biomarkers; Hypertension, Portal; Leukocyte L1 Antigen Complex; Liver Cirrhosis; Prognosis
PubMed: 37849372
DOI: 10.1111/eci.14111 -
Journal of Oral Pathology & Medicine :... Nov 2023CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its... (Review)
Review
BACKGROUND
CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its translocation into cytoplasm and nucleus could trigger cell proliferation, inhibition of apoptosis, invasion and migration of the tumour cell.
MATERIALS AND METHODS
Five electronic databases including MEDLINE by PubMed, Google scholar, Scopus, Trip, Cochrane library and EMBASE until 1 January 2023 without period restriction were thoroughly searched. Those articles that identified CTNNB1 mutation and beta catenin in odontogenic lesions were included for review. Risk of bias was analysed for each study using QUADAS 2 tool and Review Manager 5.3 was used to output its result.
RESULTS
Thirty four published articles were included for data synthesis. A total of 1092 cases of odontogenic lesions were assessed for both CTNNB1 mutation and beta catenin expression. CTNNB1 mutation was observed in ameloblastoma, calcifying odontogenic cyst, calcifying cystic odontogenic tumour and all malignant odontogenic tumours. The beta catenin expression (nuclear and cytoplasmic) was maximum in odontogenic keratocyst and calcifying odontogenic cyst. The expression was variable in ameloblastomas, membranous in odontomas, calcifying cystic odontogenic tumour and nuclear in all malignant tumours.
DISCUSSION AND CONCLUSION
High recurrence of odontogenic keratocyst and aggressiveness of solid ameloblastoma and malignant odontogenic tumours could be associated with the nuclear translocation of beta catenin. Disparity between CTNNB1 mutation and beta catenin expression within odontogenic lesions suggests alternate routes of beta catenin activation. The review results support the unique localisation of beta catenin as a helpful diagnostic factor in the pathogenesis of odontogenic lesions.
Topics: Humans; Ameloblastoma; beta Catenin; Odontogenic Cyst, Calcifying; Odontogenic Cysts; Odontogenic Tumors
PubMed: 37840228
DOI: 10.1111/jop.13487 -
Molecular Nutrition & Food Research Dec 2023Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral...
Systematic Review and Quantitative Data Synthesis of Peripheral Blood Mononuclear Cell Transcriptomics Reveals Consensus Gene Expression Changes in Response to a High Fat Meal.
SCOPE
Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no clear consensus on postprandial gene expression and protein changes in these cells.
METHOD AND RESULTS
The study systematically reviews the literature reporting transcriptional and proteomic changes in PBMCs after consumption of a high fat meal. After re-analysis of the raw data to ensure equivalence between studies, ≈85 genes are significantly changed (defined as in the same direction in ≥3 studies) with about half involved in four processes: inflammation/oxidative stress, GTP metabolism, apoptosis, and lipid localization/transport. For meals consisting predominantly of unsaturated fatty acids (UFA), notable additional processes are phosphorylation and glucocorticoid response. For saturated fatty acids (SFA), genes related to migration/angiogenesis and platelet aggregation are also changed.
CONCLUSION
Despite differences in study design, common gene changes are identified in PBMCs following a high fat meal. These common genes and processes will facilitate definition of the postprandial transcriptome as part of the overall postcibalome, linking all molecules and processes that change in the blood after a meal.
Topics: Dietary Fats; Transcriptome; Leukocytes, Mononuclear; Consensus; Proteomics; Meals; Postprandial Period; Cross-Over Studies; Triglycerides
PubMed: 37817369
DOI: 10.1002/mnfr.202300512 -
Lipids in Health and Disease Sep 2023Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C.
METHODS
The database "Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM" were retrieved to identify the literature. The quality of the selected literature was evaluated using the "the Newcastle-Ottawa Scale" (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by "Cochran's Q and I", with I ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used "Funnel plots", "Egger's tests" and "Begg's tests" to evaluate biases in the literature.
RESULTS
The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467-29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger's and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable.
CONCLUSIONS
Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.
Topics: Humans; Carrier Proteins; Fatty Liver; Genotype; Hepacivirus; Hepatitis C
PubMed: 37726765
DOI: 10.1186/s12944-023-01916-x -
Mutation Research. Reviews in Mutation... 2023The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than... (Review)
Review
The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.
Topics: Humans; Gene Expression Profiling; Transcriptome; RNA; Apoptosis; DNA Damage
PubMed: 37657754
DOI: 10.1016/j.mrrev.2023.108467 -
International Journal of Molecular... Jun 2023Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to... (Meta-Analysis)
Meta-Analysis Review
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to differentiate MCL from other NHL types; however, recently, there has been an increase in the number of reported cases of CD10-positive MCL. This warrants further investigation into this rarer immunophenotype and its clinical significance. BCL6, which is a master transcription factor for the regulation of cell proliferation and key oncogene in B cell lymphomagenesis, has been reported to have co-expression with CD10 in MCL. The clinical significance of this aberrant antigen expression remains unknown. We conducted a systematic review by searching four databases and selected five retrospective analyses and five case series. Two survival analyses were conducted to determine if BCL6 positivity conferred a survival difference: 1. BCL6+ vs. BCL6- MCL. 2. BCL6+/CD10+ vs. BCL6-/CD10+ MCL. Correlation analysis was conducted to determine if BCL6 positivity correlated with the Ki67 proliferation index (PI). Overall survival (OS) rates were performed by the Kaplan-Meier method and log-rank test. Our analyses revealed that BCL6+ MCL had significantly shorter overall survival (median OS: 14 months vs. 43 months; = 0.01), BCL6+/CD10+ MCL had an inferior outcome vs. BCL6+/CD10- MCL (median OS: 20 months vs. 55 months = 0.1828), BCL6+ MCL had significantly higher percentages of Ki67% (Ki67% difference: 24.29; = 0.0094), and BCL6 positivity had a positive correlation with CD10+ status with an odds ratio 5.11 (2.49, 10.46; = 0.0000286). Our analysis showed that BCL6 expression is correlated with CD10 positivity in MCL, and BCL6 expression demonstrated an inferior overall survival. The higher Ki67 PI in BCL6+ MCL compared to BCL6- MCL further supports the idea that the BCL6+ immunophenotype may have prognostic value in MCL. MCL management should consider incorporating prognostic scoring systems adjusted for BCL6 expression. Targeted therapies against BCL6 may offer potential therapeutic options for managing MCL with aberrant immunophenotypes.
Topics: Humans; Adult; Lymphoma, Mantle-Cell; Neprilysin; Proto-Oncogene Proteins c-bcl-6; Retrospective Studies; Prognosis; Ki-67 Antigen
PubMed: 37373354
DOI: 10.3390/ijms241210207 -
Reviews in Medical Virology Sep 2023Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) associated with susceptibility and severity of coronavirus disease 2019... (Meta-Analysis)
Meta-Analysis Review
Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) associated with susceptibility and severity of coronavirus disease 2019 (COVID-19). However, identified SNPs are inconsistent across studies, and there is no compelling consensus that COVID-19 status is determined by genetic factors. Here, we conducted a systematic review and meta-analysis to determine the effect of genetic factors on COVID-19. A random-effect meta-analysis was performed to estimate pooled odds ratios (ORs) of SNP effects, and SNP-based heritability (SNP-h ) of COVID-19. The analyses were performed using meta-R package, and Stata version 17. The meta-analysis included a total of 96,817 COVID-19 cases and 6,414,916 negative controls. The meta-analysis showed that a cluster of highly correlated 9 SNPs (R > 0.9) at 3p21.31 gene locus covering LZTFL1 and SLC6A20 genes was significantly associated with COVID-19 severity, with a pooled OR of 1.8 [1.5-2.0]. Meanwhile, another 3 SNPs (rs2531743-G, rs2271616-T, and rs73062389-A) within the locus was associated with COVID-19 susceptibility, with pooled estimates of 0.95 [0.93-0.96], 1.23 [1.19-1.27] and 1.15 [1.13-1.17], respectively. Interestingly, SNPs associated with susceptibility and SNPs associated with severity in this locus are in linkage equilibrium (R < 0.026). The SNP-h on the liability scale for severity and susceptibility was estimated at 7.6% (Se = 3.2%) and 4.6% (Se = 1.5%), respectively. Genetic factors contribute to COVID-19 susceptibility and severity. In the 3p21.31 locus, SNPs that are associated with susceptibility are not in linkage disequilibrium (LD) with SNPs that are associated with severity, indicating within-locus heterogeneity.
Topics: Humans; Genetic Predisposition to Disease; Genome-Wide Association Study; COVID-19; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Membrane Transport Proteins
PubMed: 37303119
DOI: 10.1002/rmv.2466 -
Neuroscience and Biobehavioral Reviews Sep 2023Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction,... (Review)
Review
Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.
Topics: Humans; Cocaine-Related Disorders; Depression; Brain-Derived Neurotrophic Factor; Anxiety; Anxiety Disorders; Cocaine; Serotonin Plasma Membrane Transport Proteins
PubMed: 37271299
DOI: 10.1016/j.neubiorev.2023.105270 -
Orphanet Journal of Rare Diseases May 2023Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease caused by variants in the SLC34A2 gene encoding the sodium-dependent phosphate... (Review)
Review
Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease caused by variants in the SLC34A2 gene encoding the sodium-dependent phosphate transport protein 2B, NaPi-2b. PAM is characterized by deposition of calcium phosphate crystals in the alveoli. Onset and clinical course vary considerably; some patients remain asymptomatic while others develop severe respiratory failure with a significant symptom burden and compromised survival. It is likely that PAM is under-reported due to lack of recognition, misdiagnosis, and mild clinical presentation. Most patients are genetically uncharacterized as the diagnostic confirmation of PAM has traditionally not included a genetic analysis. Genetic testing may in the future be the preferred tool for diagnostics instead of invasive methods. This systematic review aims to provide an overview of the growing knowledge of PAM genetics. Rare variants in SLC34A2 are found in almost all genetically tested patients. So far, 34 allelic variants have been identified in at least 68 patients. A majority of these are present in the homozygous state; however, a few are found in the compound heterozygous form. Most of the allelic variants involve only a single nucleotide. Half of the variants are either nonsense or frameshifts, resulting in premature termination of the protein or decay of the mRNA. There is currently no cure for PAM, and the only effective treatment is lung transplantation. Management is mainly symptomatic, but an improved understanding of the underlying pathophysiology will hopefully result in development of targeted treatment options. More standardized data on PAM patients, including a genetic diagnosis covering larger international populations, would support the design and implementation of clinical studies to the benefit of patients. Further genetic characterization and understanding of how the molecular changes influence disease phenotype will hopefully allow earlier diagnosis and treatment of the disease in the future.
Topics: Humans; Lung Diseases; Lung; Calcinosis; Frameshift Mutation; Pulmonary Alveoli; Genetic Diseases, Inborn; Sodium-Phosphate Cotransporter Proteins, Type IIb
PubMed: 37259144
DOI: 10.1186/s13023-023-02712-7 -
Medicina (Kaunas, Lithuania) May 2023: Colchicine has been proposed as a cytokine storm-blocking agent for COVID-19 due to its efficacy as an anti-inflammatory drug. The findings of the studies were... (Review)
Review
: Colchicine has been proposed as a cytokine storm-blocking agent for COVID-19 due to its efficacy as an anti-inflammatory drug. The findings of the studies were contentious on the role of colchicine in preventing deterioration in COVID-19 patients. We aimed to evaluate the efficacy of colchicine in COVID-19-hospitalized patients. : A retrospective observational cohort study was carried out at three major isolation hospitals in Alexandria (Egypt), covering multiple centers. In addition, a systematic review was conducted by searching six different databases for published studies on the utilization of colchicine in patients with COVID-19 until March 2023. The primary outcome measure was to determine whether colchicine could decrease the number of days that the patient needed supplemental oxygen. The secondary outcomes were to evaluate whether colchicine could reduce the number of hospitalization days and mortality rate in these patients. : Out of 515 hospitalized COVID-19 patients, 411 were included in the survival analysis. After adjusting for the patients' characteristics, patients not receiving colchicine had a shorter length of stay (median: 7.0 vs. 6.0 days) and fewer days of supplemental oxygen treatment (median: 6.0 vs. 5.0 days), < 0.05, but there was no significant difference in mortality rate. In a subgroup analysis based on oxygen equipment at admission, patients admitted on nasal cannula/face masks who did not receive colchicine had a shorter duration on oxygen supply than those who did [Hazard Ratio (HR) = 0.76 (CI 0.59-0.97)]. Using cox-regression analysis, clarithromycin compared to azithromycin in colchicine-treated patients was associated with a higher risk of longer duration on oxygen supply [HR = 1.77 (CI 1.04-2.99)]. Furthermore, we summarized 36 published colchicine studies, including 114,878 COVID-19 patients. COVID-19-hospitalized patients who were given colchicine had poorer outcomes in terms of the duration of supplemental oxygen use and the length of their hospital stay. Therefore, based on these findings, the use of colchicine is not recommended for COVID-19-hospitalized adults.
Topics: Adult; Humans; COVID-19; Colchicine; Retrospective Studies; SARS-CoV-2; Oxygen Saturation; Oxygen; Observational Studies as Topic
PubMed: 37241167
DOI: 10.3390/medicina59050934