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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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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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Leucemia Linfocítica Crônica de Células B , Masculino , Humanos , Feminino , Leucemia Linfocítica Crônica de Células B/genética , Cadeias HLA-DRB1 , Cadeias HLA-DRB3 , Romênia/epidemiologia , Polimorfismo Genético/genética , Antígenos HLA-ARESUMO
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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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
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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Complexo de Golgi , Imunidade Inata , Inflamassomos , Autofagossomos , Caspase 1RESUMO
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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Frequência do Gene , Antígenos HLA-A , Antígenos HLA-B , Antígenos HLA-C , Doadores de Tecidos , Humanos , Antígenos HLA-C/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Masculino , Feminino , Alelos , Romênia , Células-Tronco Hematopoéticas/metabolismo , Transplante de Células-Tronco Hematopoéticas , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade/métodos , Genótipo , Pessoa de Meia-IdadeRESUMO
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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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Trombocitopenia , Humanos , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepacivirus , Estudos Retrospectivos , Ascite/induzido quimicamente , Ascite/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológicoRESUMO
Hepatitis C virus (HCV)-infected individuals may have a faster progression of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development when influenced by host, viral and environmental factors. Hepatitis C virus disease progression is also associated with genetic variants of specific killer cell immunoglobulin-like receptors (KIRs) and genes of the major histocompatibility complex (MHC). The aim of the present study was to correlate clinical, virologic and biochemical parameters and to evaluate the possible influence of KIR genes and their HLA class I ligands in patients infected with hepatitis C virus. The present study analysed a total of 127 chronic HCV-infected patients for various biochemical and genetics factors that can influence disease progression and prognosis. Liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), direct bilirubin (DB), alpha-fetoprotein (AFP), HCV RNA levels and fibrosis indices were analysed using well-established biochemical methods. At the same time, KIR and HLA genotyping was performed using a polymerase chain reaction sequence-specific primer technique. Analysis of HLA class I and HLA ligands revealed that HLA-C*12:02 and HLA-A3 and HLA-A11 were positively associated with the F3-F4 fibrosis group (p = .026; OR = 8.717, CI = 1.040-73.077; respectively, p = .047; OR = 2.187; 95% CI = 1.066-4.486). KIR2DL2-positive patients had high median levels of AST after treatment and direct bilirubin levels when compared to KIR2DL2-negative patients (p = .013, respectively, p = .028). KIR2DL2/KIR2DL2-C1C1 genotype was associated with increased AST, ALT and GGT levels. A higher GGT level was also observed in KIR2DS2-C1-positive patients when compared to KIR2DS2-C1-negative patients. The present research demonstrates several links between specific clinical, virologic and biochemical parameters and the expression of KIR genes and their HLA ligands in HCV-infected patients. These connections should be taken into account when considering disease development and treatment.
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Hepatite C Crônica/imunologia , Receptores KIR/genética , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Comorbidade , Progressão da Doença , Feminino , Genótipo , Antígenos HLA-A/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/enzimologia , Hepatite C Crônica/genética , Humanos , Ligantes , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Receptores KIR2DL2/genética , Romênia , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: Chronic renal insufficiency (CRI) is a global public health problem with a high incidence in the Romanian population. In this study, we aimed to investigate genomic HLA polymorphisms in Romanian patients with CRI waiting for kidney transplantation. To determine the existence of a potential strong link between certain HLA polymorphisms and CRI, we also looked at HLA specificity combinations within the same locus or even different loci, referring to randomly inherited allelic combinations rather than potential haplotypes. METHODS: A total of 2199 patients with CRI on the kidney transplantation waiting list were included. A total of 2786 healthy individuals were included as controls. Both patients and controls were assessed for both HLA I and class II genes. HLA genes were typed using the low-resolution method polymerase chain reaction sequence-specific primer. RESULTS: Certain class I and class II HLA allele groups, genotypes and haplotypes were significantly more frequent in patients with CRI than in the control individuals (eg B* 40 (p ≤ .001, pc ≤ .001), C* 12 (p ≤ .001, pc ≤ .001), DRB1*14 (p = .0022, pc = .04), C*12,- (p < .001, pc < .001), A*01-C*15 (p = .0003, pc = .03) and A*02-C*12 (p = .0005, pc = .0486)). CONCLUSIONS: HLA gene polymorphisms could be clinically relevant CRI-associated genetic profiles in Romanian patients with CRI.
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Antígenos HLA/genética , Polimorfismo Genético , Insuficiência Renal Crônica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Haplótipos , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/terapia , Romênia , Adulto JovemRESUMO
BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/virologia , 2-Naftilamina , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/uso terapêutico , Carbamatos/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Lactamas Macrocíclicas , Modelos Logísticos , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prolina/análogos & derivados , Estudos Prospectivos , Ribavirina/uso terapêutico , Romênia , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Uracila/análogos & derivados , Uracila/uso terapêutico , ValinaRESUMO
Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.
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Hepatopatias/cirurgia , Transplante de Fígado , Doadores Vivos , Listas de Espera , Adolescente , Adulto , Idoso , Cadáver , Criança , Pré-Escolar , Doença Hepática Terminal/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Lactente , Comunicação Interdisciplinar , Hepatopatias/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Romênia , Resultado do TratamentoRESUMO
Knowledge of human leukocyte antigen (HLA) allele frequencies is essential for bone marrow and kidney donor searches. The Romanian Caucasian population is heterogeneous and information on HLA polymorphism has not been well studied. We characterized the HLA genetic profile and allele frequencies of regional populations in Romania. HLA-A, B and DRB1 alleles were examined in 8252 individuals, belonging to the four main regions of Romania. The most common alleles found in the Romanian population are the following: HLA-A*01, A*02, A*03, A*11, A*24; HLA-B*18, B*35, B*44, B*51 and HLA-DRB1*01, DRB1*03, DRB1*07, DRB1*11, DRB1*13, DRB1*15, DRB1*16. More than half of the alleles are non-homogeneously spread in Romania. These results provide a starting point for future analyses of genetic heterogeneity in Romania.
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Alelos , Frequência do Gene , Genética Populacional , Antígenos HLA/genética , Análise por Conglomerados , Ligação Genética , Geografia , Humanos , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , RomêniaRESUMO
BACKGROUND: Several associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations, but with significant variations across different ethnic groups. The aim of our study was to search specific HLA-DRB1, -DQA1 and -DQB1 polymorphisms that are associated with JIA and different disease phenotypes in Romanian patients compared with other ethnic groups. METHODS: HLA genotyping was performed in 61 JIA patients and 30 ethnicity-matched controls using molecular biology methods, PCR-SSOP. RESULTS: A protective effect across the whole cohort was observed for HLA-DRB1*15 (OR = 0.179, 95% CI: 0.054 -0.58) and HLA-DQB1*06 (OR = 0.285, 95% CI: 0.11-0.72). Each ILAR subgroup had a characteristic pattern of HLA associations. Unlike other populations, we found a positive association of HLA-DQA1*03 with chronic uveitis (OR = 14.67, 95% CI: 1.5-143) and a negative association of HLA-DQA1*01 with early disease onset (OR = 0.175, 95% CI: 0.036- 0.862), suggesting that the HLA-DR/DQ profile can affect the clinical expression of the disease. CONCLUSIONS: The study reveals multiple HLA-DR/DQ associations with JIA, not only similar with those found in other populations, but also some distinctive associations. However, some of the previously established associations were not replicated in Romanian patients. These results might be due to the small size of our cohort or to true population differences.
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Artrite Juvenil/imunologia , Antígenos HLA/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Adulto JovemRESUMO
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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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: 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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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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Neoplasias Hepáticas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , MicroRNAs/genética , Estudos de Casos e Controles , Hepatopatia Gordurosa não Alcoólica/metabolismo , Biomarcadores , Neoplasias Hepáticas/complicaçõesRESUMO
[This corrects the article DOI: 10.3389/fendo.2024.1349524.].
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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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Transtornos Linfoproliferativos , Neoplasias , Humanos , Romênia , Estudos de Casos e Controles , Antígenos HLA-C , Cadeias HLA-DRB1 , Imunogenética , Antígenos HLA-B , Antígenos HLA-ARESUMO
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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Infecções por HIV , Falência Renal Crônica , Transplante de Rim , Humanos , Feminino , Adulto , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Falência Renal Crônica/cirurgia , Falência Renal Crônica/complicações , Romênia , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Tacrolimo/uso terapêutico , Interações MedicamentosasRESUMO
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.