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Background: Hepatitis B Virus (HBV) can affect life quality. Monitoring and understanding the fluctuations of the HBV level of viremia related to the intricate immune activity of the host helps in the development of new treatment strategies and evaluation patterns. This meta-analysis presents the correlations between cytokines and the level of viremia in chronic HBV patients for a better comprehension of the immune mechanisms behind this infection. Methods: We used PRISMA guidelines for this meta-analysis. The databases assessed were PUBMED, WEB OF SCIENCE, SCOPUS, and Cochrane Library. ZOTERO and PlotDigitizer helped the systematic research process. We extracted information related to the correlations between cytokines and the HBV-DNA level. Effect measures included comparisons between standardized mean differences and correlation coefficients. We evaluated retrieved articles with the Newcastle-Ottawa Quality Assessment Scale (NOS). The R 4.2.2 software displayed the statistical calculation and graphical representations. Results: From 58,169 records, we extracted 16 articles with 32 different cytokine determinations. The main interleukins included in detection panels were IL-10 and IL-21. The meta-correlation analysis comprised 1,199 chronic HBV patients. The standardized mean difference between cytokine levels in HBV patients and healthy controls was 0.82 (95% CI = [-0.19, 1.84], p = 0.11). We observed a significant, fair, pooled correlation coefficient between IL-10, IL-9, and the viral load (r = 0.52, 95% CI = [0.19, 0.85]). Conclusion: This meta-analysis brings novelty because it gives a first rigorous systematic look at multiple studies with many cytokines. Our research approaches a debatable issue and gives a possible solution for settling controversies. Future studies can arise towards understanding the immune disruption in HBV and the development of new, improved assays for prognosis.
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Scientists study the molecular activities of the hepatitis B virus (HBV). However, in vivo experiments are scarce. Some microRNAs are HBV-related, but their exact mechanisms are unknown. Our study provides an up-to-date view of the associations between microRNAs and HBV-DNA levels in chronically infected individuals. We conducted this large-scale research on five databases according to PRISMA guidance. Joanna Briggs Institute tools and Newcastle Ottawa Quality Assessment scores helped with quality evaluations. R 4.2.2 performed statistical computations for the meta-analysis. DIANA-microT 2023 and g:Profiler enriched the predictions of liver genes associated with miR-122 and miR-192-5p. From the 1313 records, we eliminated those irrelevant to our theme, non-article methodologies, non-English entries, and duplicates. We assessed associations between microRNAs and HBV-DNA levels. Overall, the pooled correlations favoured the general idea of the connection between non-coding molecules and viremia levels. MiR-122 and miR-192-5p were the most researched microRNAs, significantly associated with HBV-DNA levels. The connections between miR-122, miR-192-5p, let-7, miR-215, miR-320, and viral loads need further in vivo assessment. To conclude, this study evaluates systematically, for the first time, the correlations between non-coding molecules and viremia levels in patients. Our meta-analysis emphasizes potentially important pathways toward new inhibitors of the viral replication cycle.
Assuntos
DNA Viral , Vírus da Hepatite B , Hepatite B Crônica , MicroRNAs , Carga Viral , MicroRNAs/genética , Humanos , Hepatite B Crônica/virologia , Hepatite B Crônica/genética , Vírus da Hepatite B/genética , DNA Viral/genéticaRESUMO
Background: The detection of fibrosis remains a necessity for the evaluation of hepatitis B virus (HBV)-infected patients, but the most accurate technique is invasive. Current studies aim to develop a novel noninvasive biomarker for fibrosis assessment, but no-one has found the ideal candidate. This study is a meta-analysis combined with a pilot study to investigate the connection between two transferase compounds and the levels of fibrosis. Methods: We studied data from PUBMED, Web of Science, and Scopus, retrieving 28,896 articles. Following PRISMA guidelines, we finally analyzed full-text articles written in English. The excluded items were duplicates, non-article entries, and irrelevant papers. We assessed the variations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels between patients with high and low levels of fibrosis. Joanna Briggs Institute tools were used to assess article quality. We used R 4.2.2 for statistics. The pilot study included 14 randomly chosen patients with different fibrosis levels. Results: We found significant differences in ALT and GGT levels between patients with high and low fibrosis. The GGT/ALT ratio correlated with the levels of fibrosis and the fibrosis-4 (FIB-4) score. Conclusions: This meta-analysis assessed ALT and GGT levels in chronic HBV patients with fibrosis. The pilot study identified the first association between fibrosis and the GGT/ALT ratio in a Romanian cohort of chronic patients. This brings new ideas for future research.
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The HBV (hepatitis B virus) infection is intended for elimination, but evaluating patients is both costly and insufficiently applied in several countries. An expensive analysis in Romania is HBV-DNA quantification, with a limited prognostic potential. Our study intended to find new predictors for high viremia in HBV patients, using molecules involved in the multiple assessment of various HBV complications, such as microRNAs. A total of 61 subjects (48 patients with chronic HBV infection and 13 healthy subjects) were generally evaluated. Using a RT-PCR method, with a 2-ΔΔCT algorithm, we detected the expressions of miR-122 and miR-146a in 33 subjects. MiR-21 was the internal control. The results were analyzed with the R 4.2.2. software. Kruskal-Wallis's comparisons, Spearman correlations, and several logistic regression methods were applied. The median age of the patients was over 40 years. Without microRNAs, we could not obtain a good prediction formula. The combination of miR-122 and age proved to be the best prediction method for high viremia, with an AUC of 0.827, and a sensitivity of 89.5%. This is the first study which included age and miR-122 as independent predictors for high viremia in Romanian HBV-positive patients. MiR-122 is a new potential biomarker in the evaluation of Romanian patients.
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New molecular predictors for the response to treatment in HBV (hepatitis B virus) infection are assessed. Among them is miR-122. Our article searches the connection between miR-122 and the counts of lymphocytes in chronic HBV patients receiving treatment. We included the sera of 38 Romanian subjects with chronic HBV infection (20 receiving treatment and 18 not receiving treatment) and 5 healthy controls. The expression of miR-122 was determined using RT-PCR (real-time PCR) and a 2-ΔΔCT method. Two systematic analyses were also performed on databases (PUBMED, Web of Science, and Science Direct), eliminating systematic reviews, editorials, letters to editors, meta-analyses, reviews, conference proceedings, or pre-print manuscripts. We included human-based articles following the PRISMA criteria and the Newcastle Ottawa Assessment Scale for Case-Control and Cohort studies. R 4.2.2 was used for statistics, and MIENTURNET and STRING were used for the bioinformatic analysis. Our results showed a link between the variations in the expression of miR-122 and the counts of lymphocytes in HBV Romanian patients receiving therapy. Treatment influenced miR-122 and the lymphocyte numbers. This is the first study with these results, and it may lead to a new perspective on the inter-relationships between microRNAs and therapy in HBV patients.
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A current major healthcare problem is represented by antibiotic resistance, mainly due to multidrug resistant (MDR) Gram negative bacilli (GNB), because of their extended spread both in hospital facilities and in the community's environment. The aim of this study was to investigate the virulence traits of Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa MDR, XDR, and PDR strains isolated from various hospitalized patients. These GNB strains were investigated for the presence of soluble virulence factors (VF), such as hemolysins, lecithinase, amylase, lipase, caseinase, gelatinase, and esculin hydrolysis, as well as for the presence of virulence genes encoding for VF involved in adherence (TC, fimH, and fimA), biofilm formation (algD, ecpRAB, mrkA, mrkD, ompA, and epsA), tissue destruction (plcH and plcN), and in toxin production (cnfI, hlyA, hlyD, and exo complex). All P. aeruginosa strains produced hemolysins; 90% produced lecithinase; and 80% harbored algD, plcH, and plcN genes. The esculin hydrolysis was detected in 96.1% of the K. pneumoniae strains, whereas 86% of them were positive for the mrkA gene. All of the A. baumannii strains produced lecithinase and 80% presented the ompA gene. A significant association was found between the number of VF and the XDR strains, regardless of the isolation sources. This study opens new research perspectives related to bacterial fitness and pathogenicity, and it provides new insights regarding the connection between biofilm formation, other virulence factors, and antibiotic resistance.
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Salt diapirism is often associated with potential hydrocarbon energy resources, and detecting active diapirs can strongly affect the prospect to discover new gas and oilfields. Here we use InSAR techniques as a proxy to evaluate surface deformation in the Diapiric Fold Zone located in the East Carpathians Bend. Significant surface uplift (~ 5 mm/year) is identified in a relatively small region not previously known for the presence of an actively rising salt diapir. Using high-resolution two-dimensional thermomechanical numerical simulations of salt diapirs intrusions, we show that that the observed surface deformation can be induced by a relatively small salt diapir (1-2 km in diameter) rising from an initial salt layer located at < 7 km depth. We constrain the salt diapir viscosity by comparing the InSAR surface deformation pattern with results from numerical simulations and our best fitting model is obtained for a salt viscosity of 1 × 1017 Pa s. The best fitting model reveals the presence of a relatively small salt diapir that has not pierced yet the entire sedimentary layer and is located just 1-2 km below the surface.
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Dual subduction represents an unusual case of subduction where one oceanic plate subducts on top of another, creating a highly complex tectonic setting. Because of the complex interaction between the two subducted plates, the origin of seismicity in such region is still not fully understood. Here we investigate the thermal structure of dual subduction beneath Kanto, central Japan formed as a consequence of a unique case of triple trench junction. Using high-resolution three-dimensional thermo-mechanical models tailored for the specific dual subduction settings beneath Kanto, we show that, compared with single-plate subduction systems, subduction of double slabs produces a strong variation of mantle flow, thermal and fluid release pattern that strongly controls the regional seismicity distribution. Here the deepening of seismicity in the Pacific slab located under the Philippine Sea slab is explained by delaying at greater depths (~150 km depth) of the eclogitization front in this region. On the other hand, the shallower seismicity observed in the Philippine Sea slab is related to a young and warm plate subduction and probably to the presence of a hot mantle flow traveling underneath the slab and then moving upward on top of the slab.
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For some volcanic arcs, the geochemistry of volcanic rocks erupting above subducted oceanic fracture zones is consistent with higher than normal fluid inputs to arc magma sources. Here we use enrichment of boron (B/Zr) in volcanic arc lavas as a proxy to evaluate relative along-strike inputs of slab-derived fluids in the Aleutian, Andean, Cascades and Trans-Mexican arcs. Significant B/Zr spikes coincide with subduction of prominent fracture zones in the relatively cool Aleutian and Andean subduction zones where fracture zone subduction locally enhances fluid introduction beneath volcanic arcs. Geodynamic models of subduction have not previously considered how fracture zones may influence the melt and fluid distribution above slabs. Using high-resolution three-dimensional coupled petrological-thermomechanical numerical simulations of subduction, we show that enhanced production of slab-derived fluids and mantle wedge melts concentrate in areas where fracture zones are subducted, resulting in significant along-arc variability in magma source compositions and processes.