Journal of Personalized Medicine

Research

12 pages, 967 KiB

Open AccessArticle

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension

by Renata Grzywa-Czuba, Joanna Beata Trojanek, Jacek Michałkiewicz, Izabela Kubiszewska, Łukasz Obrycki, Aldona Wierzbicka-Rucińska and Mieczysław Litwin

J. Pers. Med. 2024, 14(3), 255; https://doi.org/10.3390/jpm14030255 - 28 Feb 2024

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Abstract

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in [...] Read more.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = −0.49), systolic blood pressure (SBP) (−0.44), and carotid intima-media thickness (cIMT) (−0.43). The IGF-1R expression was negatively correlated with PWV (r = −0.42) and SBP (r = −0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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12 pages, 2252 KiB

Open AccessArticle

Histopathological Clues of Enhanced Inflammation in the Placental Tissue of Women with Chronic Venous Disease in Lower Limbs during Pregnancy

by María Asunción Sánchez-Gil, Oscar Fraile-Martinez, Cielo García-Montero, María Del Val Toledo, Luis G. Guijarro, Juan A. De León-Luis, Coral Bravo, Raúl Díaz-Pedrero, Laura López-Gonzalez, Miguel A. Saez, Melchor Álvarez-Mon, Natalio García-Honduvilla and Miguel A. Ortega

J. Pers. Med. 2024, 14(1), 87; https://doi.org/10.3390/jpm14010087 - 12 Jan 2024

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Abstract

It is estimated that approximately one in three women develop chronic venous disease (CVD) during pregnancy, a broad spectrum of morphofunctional disorders affecting the venous system in different regions of the body, including the lower limbs. A growing body of evidence supports the [...] Read more.

It is estimated that approximately one in three women develop chronic venous disease (CVD) during pregnancy, a broad spectrum of morphofunctional disorders affecting the venous system in different regions of the body, including the lower limbs. A growing body of evidence supports the diverse maternofetal consequences derived from this condition, with the placenta being an organ particularly affected. Among other consequences, having CVD during pregnancy has been associated with systemic inflammation and altered cytokines and chemokine profiles in the maternal and fetal serum related to this condition. In the present work, we aimed to analyze if these inflammatory changes also occurred in the placental tissue of women with CVD, exploring by immunohistochemistry and real-time PCR (RT-qPCR) gene and protein expression of critical inflammatory markers like allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A, and IL-18. Our results demonstrate an enhanced tissue expression of AIF-1, IL-12A, and IL-18, accompanied by a decrease in IL-10 in the placentas of women who had undergone CVD during pregnancy. Overall, our results suggest a possible pathophysiological role of inflammation in the placental tissue of women with CVD during pregnancy, although the precise consequences of this feature remain to be deeply analyzed. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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12 pages, 1356 KiB

Open AccessArticle

Inflammatory Determinants and Associated Morbidity in Hemodialysis Patients

by Claudia Jackelin De la Cruz-Ahumada, Jorge Fernando Topete-Reyes, Juan Pablo Mena-Ramírez, Juan Manuel Guzmán-Flores, Jesúa Ivan Guzmán-González and Saúl Ramírez-De los Santos

J. Pers. Med. 2023, 13(9), 1311; https://doi.org/10.3390/jpm13091311 - 27 Aug 2023

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Abstract

Hemodialysis deteriorates patients’ physical, metabolic, and mental status. Clinical outcomes derived from inflammation determine a worse status but are less frequently identified. The objective of the study was to identify inflammatory determinants and the effect of SNP-related serum IL-6 and IL-10 levels on [...] Read more.

Hemodialysis deteriorates patients’ physical, metabolic, and mental status. Clinical outcomes derived from inflammation determine a worse status but are less frequently identified. The objective of the study was to identify inflammatory determinants and the effect of SNP-related serum IL-6 and IL-10 levels on associated morbidity in hemodialysis. A sample of hemodialysis patients at IMSS Regional Hospital No.46 in Guadalajara (n = 85) were tested using the Malnutrition Inflammation Score (MIS) and Patient Health Questionnaire-9 (PHQ-9) to assess the associated morbidity. Serum cytokine levels were quantified by enzyme-linked immunosorbent assay (ELISA). The restriction fragment length polymorphism (RFLP) technique was used for analysis of IL-6-572C/G and IL-10-1082A/G. Using data visualization methods, we identified relevant determinants of inflammation. A simple regression model was constructed between predictors and targets with genotypes as covariates. Results showed malnutrition in 85.9% of patients and depressive symptoms in 50.6%. IL-10 was the most relevant inflammatory determinant, with regression coefficients (R²) between 0.05 and 0.11. The GG genotype of IL-10-1082 A/G evinced small effect on both clinical outcomes (δ of 0.35 and 0.37, respectively). Hemodialysis increases the associated morbidity, cytokines act as inflammatory determinants, and genetic variability contributes to the severity of clinical outcomes. Further studies need to refine the causal relationship between inflammation and CKD. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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17 pages, 1470 KiB

Open AccessArticle

Comprehensive Molecular Evaluation of HNF-1 Alpha, miR-27a, and miR-146 Gene Variants and Their Link with Predisposition and Progression in Type 2 Diabetes Patients

by Rashid Mir, Imadeldin Elfaki, M. E. Elangeeb, Mamdoh S. Moawadh, Faris Jamal Tayeb, Jameel Barnawi, Ibrahim Altedlawi Albalawi, Amnah A. Alharbi, Marwan H. Alhelali and Basim S. O. Alsaedi

J. Pers. Med. 2023, 13(8), 1270; https://doi.org/10.3390/jpm13081270 - 17 Aug 2023

Cited by 1 | Viewed by 1210

Abstract

Background: Type 2 diabetes (T2D) is a metabolic condition induced by insulin resistance and pancreatic beta cell dysfunction. MicroRNAs (miRNAs) have biological significance because they regulate processes such as the molecular signaling pathways involved in the pathophysiology of diabetes mellitus. The hepatocyte nuclear [...] Read more.

Background: Type 2 diabetes (T2D) is a metabolic condition induced by insulin resistance and pancreatic beta cell dysfunction. MicroRNAs (miRNAs) have biological significance because they regulate processes such as the molecular signaling pathways involved in the pathophysiology of diabetes mellitus. The hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a transcription factor found in hepatocytes and the pancreas. Mutations in the HNF-1 alpha gene were reportedly associated with maturity-onset diabetes of the young (MODY). The objective of the present study was to examine the associations between MiR-27a, MiR-146, and HNF-1 alpha single-nucleotide variations (SNVs) with T2D risk in the Saudi population. Methodology: We evaluated the association of SNVs of miR-27a rs895819 A>G, 146a-rs2910164 C>G, and HNF-1 alpha rs1169288 G>T (I27L) with the risk of T2D in Saudi patients with the Amplification Refractory Mutation System PCR (ARMS-PCR). For the miR-27a SNVs, we used 115 cases (82 males, 33 females) and 117 matched healthy controls (HCs); for the Mir-146 SNVs, we used 103 cases (70 males, 33 females) and 108 matched HCs; and for the HNF-1 alpha, we employed 110 patients (80 males, 30 females) and 110 HCs. The blood biochemistry of the participants was essayed using commercial kits, and the methods of statistical analysis used were the Chi-square test, the Fisher exact test, and a multivariate analysis based on logistic regression, like the odds ratio (OD) and risk ratio (RR), with 95% confidence intervals (CIs). Results: The MiR-27a rs895819 AG genotype was linked to increased T2D susceptibility, with OR = 2.01 and p-value = 0.011, and the miR-146 rs2910164 CG genotype and C allele were linked to an elevated risk of T2D, with OR = 2.75, p-value < 0.0016, OR = 1.77, and p-value = 0.004. The results also showed that the GT genotype and T allele of the HNF-1 alpha (rs1169288) G>T is linked to T2D, with OR = 2.18, p-value = 0.0061, and 1.77, p-value = 0.0059. Conclusions: The SNVs in miR-27a, miR-146, and HNF-1 alpha can be potential loci for T2D risk. The limitations of this study include the relatively small sample size and the fact that it was a cross-sectional study. To our knowledge, this is the first study to highlight the association between miR-27a, miR-146, and HNF-1 alpha SNVs and the risk of T2D in the Saudi population. Future large-scale case–control studies, as well as studies on the functions of the proteins and protein interaction studies for HNF-1 alpha, are required to verify our findings. Furthermore, these findings can be used for the identification and stratification of at-risk populations via genetic testing for T2D-prevention strategies. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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11 pages, 298 KiB

Open AccessArticle

The Occurrence of Gluten-Related Antibodies, Sensitization to Selected Food Allergens, and Antibodies against Intrinsic Factor in Adult Patients with Diarrhea-Predominant Irritable Bowel Syndrome

by Joanna B. Bierła, Bożena Cukrowska, Barbara Skrzydło-Radomańska, Beata Prozorow-Król, Anetta Kurzeja-Mirosław, Halina Cichoż-Lach, Katarzyna Laskowska, Agnieszka Sowińska and Emilia Majsiak

J. Pers. Med. 2023, 13(7), 1165; https://doi.org/10.3390/jpm13071165 - 20 Jul 2023

Cited by 1 | Viewed by 1156

Abstract

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Due to the possible overlap of IBS clinical symptoms with gluten-related diseases, food allergies, and autoimmune gastritis (AIG), the aim of this study was to present the frequency of anti-tissue transglutaminase 2 (TTG2) [...] Read more.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Due to the possible overlap of IBS clinical symptoms with gluten-related diseases, food allergies, and autoimmune gastritis (AIG), the aim of this study was to present the frequency of anti-tissue transglutaminase 2 (TTG2) autoantibodies, anti-deamidated gluten peptide (DGP) antibodies, specific immunoglobulin E antibodies (sIgE) to selected food allergens, and anti-intrinsic factor (IF) autoantibodies in adult patients with diarrhea-predominant IBS (IBS-D). The study involved 244 patients (170 women) aged 18–75 years. The antibodies were measured with the use of multiparametric immunoassays. Elevated antibody concentrations, irrespective of the class of tested antibody, occurred in 44 patients (17.6%), including 11 patients (4.5%) with positive DGP antibodies, four patients (1.6%) with TTG2 autoantibodies, six patients (2.5%) with IF autoantibodies, and 31 patients (12.7%) with sIgE to food allergens. Sensitization to gluten, proteins from cow’s milk, and bovine serum albumin was found in 2.1%, 5.3%, and 9.0% of patients, respectively. Our study showed a high percentage of positive results for the tested antibodies in the IBD-D patients, which indicates the need to perform serological tests for CD, food allergies, and AIG in this group of patients. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

Review

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14 pages, 1482 KiB

Open AccessReview

No Association of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) Gene Polymorphism in the Susceptibility to Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients: An Updated Meta-Analysis

by Aline Ruilowa de Pinho Coelho, Luciana Carvalho Silveira, Kamilla de Faria Santos, Rodrigo da Silva Santos and Angela Adamski da Silva Reis

J. Pers. Med. 2023, 13(9), 1308; https://doi.org/10.3390/jpm13091308 - 26 Aug 2023

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Abstract

Diabetic retinopathy (DR) is a complex and multifactorial pathology encompassing environmental, metabolic, and polygenic influences. Among the genes possibly involved in the development and progression of DR, the Angiotensin I-converting enzyme (ACE) gene stands out, which presents an insertion (I) or [...] Read more.

Diabetic retinopathy (DR) is a complex and multifactorial pathology encompassing environmental, metabolic, and polygenic influences. Among the genes possibly involved in the development and progression of DR, the Angiotensin I-converting enzyme (ACE) gene stands out, which presents an insertion (I) or deletion (D) polymorphism of a 287 bp Alu repetitive sequence in intron 16. Thus, this study aimed to perform a systematic review with meta-analysis to elucidate the relationship between the ACE gene (I/D) polymorphism (rs1799752) and the development and progression of DR in type 2 diabetic patients. PubMed/MEDLINE, Embase, Web of Science, and Scopus databases were systematically searched to retrieve articles that investigated the association between ACE gene (I/D) polymorphism in DR patients. Sixteen articles were included in the systematic review. The results describe no significant association between the polymorphism and DR risk (OR = 1.12; CI = 0.96–1.31; and p = 0.1359) for genotypic analysis by the dominant model (II vs. ID+DD). Moreover, we also observed no significant association between the D allele on the allele frequency analysis (I vs. D) and the DR risk (OR = 1.10; CI = 0.98–1.23; and p = 0.1182). Forest plot analysis revealed that the discrepancy between previous studies most likely arose from variations in their sample sizes. In conclusion, I/D polymorphism appears to be not involved in the susceptibility to and progression of the DR in type 2 diabetic patients. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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Other

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6 pages, 823 KiB

Open AccessCase Report

Macro-TSH: An Uncommon Explanation for Persistent TSH Elevation That Thyroidologists Have to Keep in Mind

by Isabella Chiardi, Mario Rotondi, Marco Cantù, Franco Keller and Pierpaolo Trimboli

J. Pers. Med. 2023, 13(10), 1471; https://doi.org/10.3390/jpm13101471 - 08 Oct 2023

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Abstract

A macro-thyroid-stimulating hormone (macro-TSH) is an infrequent yet noteworthy phenomenon in the thyroid field. A 69-year-old patient presented with persistently elevated thyroid-stimulating hormone (TSH) levels ranging from 30 to 50 mIU/L, paradoxically accompanied by normal thyroid hormone levels and normal thyroid ultrasound, with [...] Read more.

A macro-thyroid-stimulating hormone (macro-TSH) is an infrequent yet noteworthy phenomenon in the thyroid field. A 69-year-old patient presented with persistently elevated thyroid-stimulating hormone (TSH) levels ranging from 30 to 50 mIU/L, paradoxically accompanied by normal thyroid hormone levels and normal thyroid ultrasound, with no findings on pituitary magnetic resonance. Laboratory studies were conducted to investigate potential interferences impacting the accuracy of TSH measurements. After excluding other potential causes, polyethylene glycol (PEG) precipitation technique was used, which led us to the diagnosis of macro-TSH. This result was confirmed through chromatography. Macro-TSH, although rare, emerged as the key contributor to the patient’s unexplained increase in TSH levels. This case highlights the importance of considering macro-TSH as a potential etiology in cases characterized by unexplained TSH elevation, offering insights into diagnostic protocols and expanding our understanding of thyroid function anomalies. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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19 pages, 952 KiB

Open AccessSystematic Review

MicroRNAs Associated with the Pathophysiological Mechanisms of Gestational Diabetes Mellitus: A Systematic Review for Building a Panel of miRNAs

by Pedro Henrique Costa Matos da Silva, Kamilla de Faria Santos, Laura da Silva, Caroline Christine Pincela da Costa, Rodrigo da Silva Santos and Angela Adamski da Silva Reis

J. Pers. Med. 2023, 13(7), 1126; https://doi.org/10.3390/jpm13071126 - 11 Jul 2023

Cited by 2 | Viewed by 1192

Abstract

miRNAs, a class of small non-coding RNAs, play a role in post-transcriptional gene expression. Therefore, this study aimed to conduct a systematic review of miRNAs associated with GDM to build a panel of miRNAs. A bibliographic search was carried out in the PubMed/Medline, [...] Read more.

miRNAs, a class of small non-coding RNAs, play a role in post-transcriptional gene expression. Therefore, this study aimed to conduct a systematic review of miRNAs associated with GDM to build a panel of miRNAs. A bibliographic search was carried out in the PubMed/Medline, Virtual Health Library (VHL), Web of Science, and EMBASE databases, selecting observational studies in English without time restriction. The protocol was registered on the PROSPERO platform (number CRD42021291791). Fifty-five studies were included in this systematic review, and 82 altered miRNAs in GDM were identified. In addition, four miRNAs were most frequently dysregulated in GDM (mir-16-5p, mir-20a-5p, mir-222-3p, and mir-330-3p). The dysregulation of these miRNAs is associated with the mechanisms of cell cycle homeostasis, growth, and proliferation of pancreatic β cells, glucose uptake and metabolism, insulin secretion, and resistance. On the other hand, identifying miRNAs associated with GDM and elucidating its main mechanisms can assist in the characterization and definition of potential biomarkers for the diagnosis and treatment of GDM. Full article

(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)

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