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Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component "Immunogenetics of Ageing" showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65-99 years) and ethnically matched young group (age 18-64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships.

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The HLA genes are associated with various autoimmune pathologies, with the control of the immune response also being significant in organs and cells transplantation. The aim of the study is to identify the HLA-A, HLA-B, and HLA-C alleles frequencies in the analyzed Romanian cohort. We performed HLA typing using next-generation sequencing (NGS) in a Romanian cohort to estimate class I HLA allele frequencies up to a six-digit resolution. A total of 420 voluntary donors from the National Registry of Voluntary Hematopoietic Stem Cell Donors (RNDVCSH) were included in the study for HLA genotyping. Peripheral blood samples were taken and brought to the Fundeni Clinical Institute during 2020-2021. HLA genotyping was performed using the Immucor Mia Fora NGS MFlex kit. A total of 109 different alleles were detected in 420 analyzed samples, out of which 31 were for HLA-A, 49 for HLA-B, and 29 for HLA-C. The most frequent HLA-A alleles were HLA-A*02:01:01 (26.11%), HLA-A*01:01:01 (12.5%), HLA-A*24:02:01 (11.67%), HLA-A*03:01:01 (9.72%), HLA-A*11:01:01, and HLA-A*32:01:01 (each with 8.6%). For the HLA-B locus, the most frequent allele was HLA-B*18:01:01 (11.25%), followed by HLA-B*51:01:01 (10.83%) and HLA-B*08:01:01 (7.78%). The most common HLA-C alleles were HLA-C*07:01:01 (17.36%), HLA-C*04:01:01 (13.47%), and HLA-C*12:03:01 (10.69%). Follow-up studies are ongoing for confirming the detected results.

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[This corrects the article DOI: 10.3389/fendo.2024.1349524.].

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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.

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Background: Hepatitis B Virus (HBV) remains a major global health challenge, with significant morbidity and mortality associated with chronic infections. Methods: This study examines the epidemiology, screening, and risk factors associated with HBV in Romania, focusing on a comprehensive national screening program, LIVE(RO)2, involving 320,000 individuals (majority of them considered vulnerable population). A questionnaire was used to collect information on the potential risk factors for HBV transmission. Results: The overall prevalence rate of HBV chronic infection among all the participants tested was 1.67% (confidence interval: 1.63-1.72%), with significant differences (p = 0.0001) between participants from the main geographical regions of residence (North-East 1.89%, South 1.38%, South-East 2.06%, and South-West 1.54%). Male persons aged 30-49 or 60-69 years old, from the rural and Eastern parts of Romania and non-Romanian ethnia, with a low level of education, unvaccinated, not married, unemployed, with family members with hepatitis, with personal histories of blood or blood product transfusion, surgical interventions, tattooing, hospitalizations, imprisonment, haemodialysis, unsafe sexual contacts, or with sexual transmitted infectious diseases were risk factors associated with HBsAg seropositivity. Conclusions: Our findings highlight significant demographic and epidemiological patterns of reduced HBV prevalence even in vulnerable persons, as well as modified risk factors and the impact of socio-economic factors.

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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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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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INTRODUCTION: Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients. CASE PRESENTATION: We present the case of a 29-year-old female patient with HIV and end-stage renal disease (ESRD) who performed a KT from a related living donor in March 2022. KT immediate evolution was favorable. No transplant-related complications were reported. HIV viral load remained undetectable and CD4+ T cells were constantly > 500 cell/ µL, during the 18 months of follow-up. The main challenge in our case was the drug interaction between the protease inhibitor-based regimen and tacrolimus. This led to tacrolimus overdose, and, subsequently, change in ARV therapy. ARV switching was performed on a regimen based on integrase inhibitor and nucleoside reverse transcriptase inhibitors. After the ARV change, the therapeutic level of tacrolimus was easily reached and maintained. Kidney graft function remained normal during follow-up, despite tacrolimus overexposure, and no rejection or anti-HLA antibodies were observed. Another challenge was related to the donor's hepatitis C virus status (positive antibodies, negative nucleic acid test). The recipient did not develop seroconversion or detectable viremia at 3-, 6-, 12- and 18-months post-KT. CONCLUSION: We reported the first case of a successful KT in an ESRD patient with HIV in Romania, in whom the post-transplant evolution was favorable.

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The Golgi apparatus, long recognized for its roles in protein processing and vesicular trafficking, has recently been identified as a crucial contributor to innate immune signaling pathways. This review discusses our expanding understanding of the Golgi apparatus's involvement in initiating and activating these pathways. It highlights the significance of membrane connections between the Golgi and other organelles, such as the endoplasmic reticulum, mitochondria, endosomes, and autophagosomes. These connections are vital for the efficient transmission of innate immune signals and the activation of effector responses. Furthermore, the article delves into the Golgi apparatus's roles in key immune pathways, including the inflammasome-mediated activation of caspase-1, the cGAS-STING pathway, and TLR/RLR signaling. Overall, this review aims to provide insights into the multifunctional nature of the Golgi apparatus and its impact on innate immunity.

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Background: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. Methods: We included 112 kidney recipients genotyped for CYP3A5*3, CYP3A4*1.001, and CYP3A4*22. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Results: Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A4*1/*1 (86.6%) and CYP3A5*3/*3 (77.7%) genotypes. CYP3A4*1.001 and CYP3A5*1 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A4*22 allele showed no such effect (p = 0.016, p < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. Conclusions: The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients.

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Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential. Markers such as vimentin, CD44, alkaline phosphatase, CD146, CD271, CD49f, Oct 3/4, Sox 9, FGF7, nestin, and BMP4 showed significant differences in expression levels, highlighting the heterogeneity and unique characteristics of each cell type. At the same time, we confirmed that all cell types successfully differentiated into osteogenic, chondrogenic, or adipose lineages, with different readiness. In conclusion, our study reveals the distinct properties and potential applications of various dental-derived stem cells. These findings contribute to a deeper understanding of OCSCs and their significance in future clinical applications.

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One of the challenges of modern-day living is to resist the temptation of overfeeding and sedentariness and maintain a healthy body and mind. On a favorable genetic and epigenetic background, a high-fat diet combined with lack of physical exercise constitutes the foundation for severe metabolic disturbances including steatotic liver disease. In our case-control study, we had the aim of establishing the role of selected micro-RNAs-miR-122, miR-192, miR-33a, and miR-33b-as superior biomarkers for the diagnosis and prognosis of steatotic liver in a 36-patient cohort compared to 12 healthy controls. Initial results confirmed the decline in miR-122 expression as fatty liver is progressing. However, combinations of ΔmiRs, such as ΔmiR33a_192, ΔmiR33a_122, and ΔmiR33b_122, correlate with ultrasound steatosis grade (R 2 = 0.78) while others such as ΔmiR33b_122 provide a high specificity and sensitivity in fatty liver disease with an area under the curve (AUC) of 0.85. Compared to classical biomarkers, micro-RNAs can be used for both diagnostic and prognostic purposes as their diminished expression in severe cases of steatosis is associated with higher risk of emerging hepatocellular carcinoma. Manipulating micro-RNAs through agomirs or antagomirs can be the answer to the yet unsolved problem of efficient therapy in MAFLD.

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BACKGROUND AND OBJECTIVES: The implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population. MATERIALS AND METHODS: This study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP). RESULTS: Several HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles. CONCLUSIONS: Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.

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Materials and Methods: This study included 66 patients with CLL, diagnosed between 2020 and 2022, and 100 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQA1/DQB1/DPA1/DPB1, and HLA-DRB1/3/4/5) were investigated using next-generation sequencing technology. Results: Several HLA alleles were strongly associated with CLL. The most important finding was that HLA-DRB1∗04:02:01 (p=0.001, OR = 1.05) and HLA-DRB3∗02:01:01 (p=0.009, OR = 1.03) have a predisposing role in CLL development. Moreover, we identified that HLA-A∗24:02:01 0.01 (p=0.01, OR = 0.38), HLA-DQA1∗05:05:01 (p=0.01, OR = 0.56), HLA-DQB1∗03:02:01 (p=0.03, OR = 0.40), and HLA-DRB4∗01:03:01 (p=0.03, OR = 0.54 alleles have protective roles. Correlations between HLA expression and gender showed that women had a higher expression of protective HLA alleles when compared to men. Conclusions: Our data are the first to indicate that in Romanian patients with CLL, the HLA-A∗24:02:01 and HLA-DQA1∗05:05:01 alleles have a protective role against CLL development, whereas HLA-DRB1∗04:02:01 and HLA-DRB3∗02:01:01alleles are positively associated with CLL.

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Hepatitis B, a persistent inflammatory liver condition, stands as a significant global health issue. In Romania, the prevalence of chronic hepatitis B virus (CHB) infection ranks among the highest in the European Union. The HLA genotype significantly impacts hepatitis B virus infection progression, indicating that certain HLA variants can affect the infection's outcome. The primary goal of the present work is to identify HLA alleles and specific amino acid residues linked to hepatitis B within the Romanian population. The study enrolled 247 patients with chronic hepatitis B; HLA typing was performed using next-generation sequencing. This study's main findings include the identification of certain HLA alleles, such as DQB1*06:03:01, DRB1*13:01:01, DQB1*06:02:01, DQA1*01:03:01, DRB5*01:01:01, and DRB1*15:01:01, which exhibit a significant protective effect against HBV. Additionally, the amino acid residue alanine at DQB1_38 is associated with a protective role, while valine presence may signal an increased risk of hepatitis B. The present findings are important in addressing the urgent need for improved methods of diagnosing and managing CHB, particularly when considering the disease's presence in diverse population groups and geographical regions.

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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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This comprehensive review article dives deep into the Golgi apparatus, an essential organelle in cellular biology. Beginning with its discovery during the 19th century until today's recognition as an important contributor to cell function. We explore its unique organization and structure as well as its roles in protein processing, sorting, and lipid biogenesis, which play key roles in maintaining homeostasis in cellular biology. This article further explores Golgi biogenesis, exploring its intricate processes and dynamics that contribute to its formation and function. One key focus is its role in neurodegenerative diseases like Parkinson's, where changes to the structure or function of the Golgi apparatus may lead to their onset or progression, emphasizing its key importance in neuronal health. At the same time, we examine the intriguing relationship between Golgi stress and endoplasmic reticulum (ER) stress, providing insights into their interplay as two major cellular stress response pathways. Such interdependence provides a greater understanding of cellular reactions to protein misfolding and accumulation, hallmark features of many neurodegenerative diseases. In summary, this review offers an exhaustive examination of the Golgi apparatus, from its historical background to its role in health and disease. Additionally, this examination emphasizes the necessity of further research in this field in order to develop targeted therapeutic approaches for Golgi dysfunction-associated conditions. Furthermore, its exploration is an example of scientific progress while simultaneously offering hope for developing innovative treatments for neurodegenerative disorders.

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In the light of recent retrovirus pandemics, the issue of discovering new and diverse RNA-specific fluorochromes for research and diagnostics became of acute importance. The great majority of nucleic acid-specific probes either do not stain RNA or cannot distinguish between DNA and RNA. The versatility of polymethine dyes makes them suitable as stains for visualization, analysis, and detection of nucleic acids, proteins, and other biomolecules. We synthesized the asymmetric dicationic homodimeric monomethine cyanine dyes 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)pyridin-1-ium) bromide (Т1) and 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium) bromide (M1) and tested their binding specificity, spectral characteristics, membrane penetration in living and fixed cells, cellular toxicity, and stability of fluorescent emission. Mesenchymal cells have diverse phenotypes and extensive proliferation and differentiation properties. We found dyes T1 and M1 to show high photochemical stability in living mesenchymal stem cells from apical papilla (SCAP) with a strong fluorescent signal when bound to nucleic acids. We found M1 to perform better than control fluorochrome (Hoechst 33342) for in vivo DNA visualization. T1, on the other hand, stains granular cellular structures resembling ribosomes in living cells and after permeabilization of the nuclear membrane stains the nucleoli and not the chromatin in the nucleus. This makes T1 suitable for the visualization of structures rich in RNA in living and fixed cells.

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Background and Objectives: To find low-cost markers that can identify the hepatitis C virus cirrhotic patients that are at risk for long-term severe adverse liver effects (ascites, ascites or upper gastrointestinal bleeding, hepatocellular carcinoma), after treatment. There is established evidence for the benefits of treating hepatitis C virus cirrhotic patients, but there is still some need for clarification concerning the real impact on the long-term evolution after achieving sustained virological response; there is no general consensus in the literature about identifying the patients that do not improve post-treatment. Materials and Methods: Our retrospective analysis investigated the long-term (2 years) evolution of 46 patients with cirrhosis with thrombocytopenia, previously infected with VHC, treated and who obtained an SVR after DAA treatment. Results: Despite the overall improvement, 8.7% patients developed hepatocellular carcinoma and 6.5% patients ascites/upper GI bleeding. We found that FIB-4, MELD and AFP changes at 1 year were the most significant predictors for these outcomes. Additionally, a drop in leukocyte count after 1 year seemed to indicate a risk for hepatocellular carcinoma, but this was not consistent. Conclusions: It might be beneficial to intensify the surveillance for post-treatment adverse liver effects for the patients with these marker changes at 1 year.

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