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Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (10 December 2021) | Viewed by 51412

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Prof. Dr. Katarzyna Komosinska-Vassev

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Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland
Interests: laboratory medicine; extracellular matrix; civilization diseases; biomarkers
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Pawel Olczyk

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Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland
Interests: biochemistry and pathobiochemistry of connective tissue
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The prevalence of diseases of civilization, i.e., cancer, diabetes, obesity, and autoimmune diseases have shown an exponential worldwide rise in recent years. The development of molecular, biotechnology, and genetic tools has provided to the clinical practice valuable diagnostic tools based on new molecules, proteins, as well as genes, which are not only involved in the pathogenesis of civilization diseases but are also used as markers to assess the effectiveness of therapy or to predict development of complications. Today, a diversity of the available diagnostic tools have helped physicians to change the way of approaching civilization illness toward the concept of personalized medicine. In this Special Issue, we invite investigators to contribute either original research or review articles focusing on the role of new protein, molecular, and genetic markers that can be used for the diagnosis and monitoring of the progression of the several complications linked to civilization diseases as well as biomarkers useful in monitoring the effects of the implemented treatment. At the same time, we invite researchers to submit either original research or review articles having civilization diseases as the main topic focusing on the latest diagnostic tools and possible use of them as biomarkers for health and disease.

Prof. Katarzyna Komosinska-Vassev
Prof. Pawel Olczyk
Guest Editors

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Keywords

Civilization diseases
Biomarkers
Health
Disease
Molecular pathways
Diagnosis
Monitoring the effects of treatment
Prediction of the development of complications

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Published Papers (12 papers)

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Research

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14 pages, 3324 KiB

Open AccessArticle

The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

by Aleksandra Mielczarek-Palacz, Celina Kruszniewska-Rajs, Marta Smycz-Kubańska, Jarosław Strzelczyk, Wojciech Szanecki, Andrzej Witek and Joanna Magdalena Gola

J. Clin. Med. 2021, 10(14), 3058; https://doi.org/10.3390/jcm10143058 - 9 Jul 2021

Cited by 5 | Viewed by 2085

Abstract

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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19 pages, 2704 KiB

Open AccessArticle

Bone Metabolism and RANKL/OPG Ratio in Rheumatoid Arthritis Women Treated with TNF-α Inhibitors

by Agnieszka Jura-Półtorak, Anna Szeremeta, Krystyna Olczyk, Aleksandra Zoń-Giebel and Katarzyna Komosińska-Vassev

J. Clin. Med. 2021, 10(13), 2905; https://doi.org/10.3390/jcm10132905 - 29 Jun 2021

Cited by 34 | Viewed by 3138

Abstract

The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (anti-TNF-α) therapy in combination with methotrexate on bone remodeling and osteoclastogenesis in female patients with RA. Serum levels of bone turnover markers (i.e., C- and N-terminal propeptides of type I procollagen (PICP and PINP), C- and N-terminal cross-linking telopeptides of type I collagen (CTX-I and NTX-I), and soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG)) were determined by immunoassay at baseline and 15 months after initiation of treatment. Bone mineral density was measured by dual-energy x-ray absorptiometry. We found a significant decrease in serum PINP levels, a biomarker of bone formation, and higher levels of CTX-I and sRANKL indicative of increased bone resorption in RA patients prior to TNFαI treatment compared to the controls. Anti-TNF-α therapy was effective in improving bone metabolism in RA patients as reflected in a decrease in CTX-I (at least partially due to the RANKL/OPG reduction) and a concomitant increase in PINP levels. The bone metabolism changes were independent of the type of TNFαI used. PINP and CTX-I were found to be useful markers of bone metabolism, which may prove the effectiveness of TNF-α therapy earlier than the bone density assessment. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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11 pages, 554 KiB

Open AccessArticle

Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines

by Yuan Zhang, Linda Johansson, Johanna Andersson-Assarsson, Magdalena Taube, Markku Peltonen, Per-Arne Svensson, Christian Herder, Anna Rudin, Lena Carlsson, Solbritt Rantapää-Dahlqvist and Cristina Maglio

J. Clin. Med. 2021, 10(13), 2791; https://doi.org/10.3390/jcm10132791 - 25 Jun 2021

Cited by 11 | Viewed by 2372

Abstract

We recently reported that increased serum adiponectin was associated with rheumatoid arthritis (RA) risk in subjects with obesity. We hereby aim to determine if other adipokines associate with RA risk and if the association between adiponectin and RA is independent of other adipokines. Two nested-case control studies were performed in two different cohorts: 82 participants of the Swedish Obese Subjects (SOS) study who developed RA during follow-up matched with 410 controls, and 88 matched pairs from the Medical Biobank of Northern Sweden. Baseline levels of circulating adipokines were measured using ELISA. In a multivariable analysis in the SOS cohort, higher adiponectin was associated with an increased risk of RA independently of other adipokines (OR for RA risk: 1.06, 95% CI: 1.01–1.12, p = 0.02). No association between leptin, resistin, and visfatin levels and the risk of RA was detected. In the cohort from the Medical Biobank of Northern Sweden, higher adiponectin was associated with an increased risk of RA only in participants with overweight/obesity (OR: 1.17, 95% CI: 1.01−1.36, p = 0.03), independently of other adipokines. Our results show that in individuals with overweight/obesity, higher circulating levels of adiponectin, but not leptin, resistin, or visfatin, were associated with an increased RA risk. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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11 pages, 2114 KiB

Open AccessArticle

Eotaxins and Their Receptor as Biomarkers of Colorectal Cancer

by Monika Zajkowska, Agnieszka Kulczyńska-Przybik, Maciej Dulewicz, Kamil Safiejko, Marcin Juchimiuk, Marzena Konopko, Leszek Kozłowski and Barbara Mroczko

J. Clin. Med. 2021, 10(12), 2675; https://doi.org/10.3390/jcm10122675 - 17 Jun 2021

Cited by 6 | Viewed by 2058

Abstract

Colorectal cancer (CRC) is one of the most common malignancies. Despite the availability of diagnostic tests, an increasing number of new cases is observed. That is why it is very important to search new markers that would show high diagnostic utility. Therefore, we made an attempt to assess the usefulness of eotaxins, as there are few studies that investigate their significance, in patients with CRC. The study included 80 subjects (CRC patients and healthy volunteers). Serum concentrations of all eotaxins were measured using a multiplexing method (Luminex), while CCR3 was measured by immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetry and classical tumor marker levels (CEA and CA 19-9) and were measured using chemiluminescent microparticle immunoassay (CMIA). The highest usefulness among the proteins tested showed CCR3. Its concentrations were significantly higher in the CRC group than in healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and the area under the ROC curve (AUC) of CCR3 were higher than those of CA 19-9. The maximum values for sensitivity, negative predictive value, and AUC were obtained for a combination of CCR3 and CRP. Our findings suggest the potential usefulness of CCR3 in the diagnosis of CRC, especially in combination with CRP or CEA. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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16 pages, 1360 KiB

Open AccessArticle

MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

by Justyna Pordzik, Ceren Eyileten-Postuła, Daniel Jakubik, Pamela Czajka, Anna Nowak, Salvatore De Rosa, Aleksandra Gąsecka, Agnieszka Cieślicka-Kapłon, Piotr Sulikowski, Krzysztof J. Filipiak, Dagmara Mirowska-Guzel, Jolanta M. Siller-Matula and Marek Postuła

J. Clin. Med. 2021, 10(11), 2371; https://doi.org/10.3390/jcm10112371 - 28 May 2021

Cited by 19 | Viewed by 3633

Abstract

MicroRNAs are endogenous non-coding RNAs that are involved in numerous biological processes through regulation of gene expression. The aim of our study was to determine the ability of several miRNAs to predict mortality and response to antiplatelet treatment among T2DM patients. Two hundred fifty-two patients with diabetes were enrolled in the study. Among the patients included, 26 (10.3%) patients died within a median observation time of 5.9 years. The patients were receiving either acetylsalicylic acid (ASA) 75 mg (65%), ASA 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by quantitative real time PCR and compared between the patients who survived and those who died. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNA expression due to different antiplatelet treatment was analyzed. After including all miRNAs into one multivariate Cox regression model, only miR-126 was predictive of future occurrence of long-term all-cause death (HR = 5.82, 95% CI: 1.3–24.9; p = 0.024). Furthermore, miR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group (p = 0.014; p = 0.013; p = 0.028, respectively). To conclude, miR-126 expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. Moreover, miR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment regimens and clinical outcomes. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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13 pages, 659 KiB

Open AccessArticle

The Diagnostic Usefulness of Circulating Profile of Extracellular Matrix Components: Sulfated Glycosaminoglycans (sGAG), Hyaluronan (HA) and Extracellular Part of Syndecan-1 (sCD138) in Patients with Crohn’s Disease and Ulcerative Colitis

by Alicja Derkacz, Paweł Olczyk, Agnieszka Jura-Półtorak, Krystyna Olczyk and Katarzyna Komosinska-Vassev

J. Clin. Med. 2021, 10(8), 1722; https://doi.org/10.3390/jcm10081722 - 16 Apr 2021

Cited by 11 | Viewed by 1932

Abstract

The described research focused on the diagnostic usefulness of sulfated glycosaminoglycans (sGAG), hyaluronan (HA), and extracellular part of syndecan-1 (sCD138) as new markers related to extracellular matrix (ECM) remodeling in the intestine during the two most common forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn’ disease (CD). Inflammatory markers belonging to ECM components were assessed in serum of patients with IBD using an immunoenzymatic method (HA and sCD138) and a method based on the reaction with dimethylmethylene blue (sulfated GAG). Measurements were carried out twice: at baseline and after one year of therapy with prednisone (patients with CD) or adalimumab (patients with UC). No quantitative changes were observed in serum sGAG, HA, and sCD138 concentrations between patients newly diagnosed with CD and the healthy group. In the case of patients with UC, the parameter which significantly differentiated healthy subjects and patients with IBD before biological therapy was HA. Significant correlation between serum HA level and inflammation activity, expressed as Mayo score, was also observed in patients with UC. Moreover, the obtained results have confirmed that steroid therapy with prednisone significantly influenced the circulating profile of all examined ECM components (sGAG, HA, and sCD138), whereas adalimumab therapy in patients with UC led to a significant change in only circulating sGAG levels. Moreover, the significant differences in serum HA levels between patients with UC and CD indicate that quantification of circulating HA may be useful in the differential diagnosis of CD and UC. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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9 pages, 673 KiB

Open AccessArticle

The Serum Concentrations of Hedgehog-Interacting Protein, a Novel Biomarker, Were Decreased in Overweight or Obese Subjects

by Hsuan-Wen Chou, Hao-Chang Hung, Ching-Han Lin, An-Chi Lin, Ye-Fong Du, Kai-Pi Cheng, Chung-Hao Li, Chih-Jen Chang, Hung-Tsung Wu and Horng-Yih Ou

J. Clin. Med. 2021, 10(4), 742; https://doi.org/10.3390/jcm10040742 - 12 Feb 2021

Cited by 4 | Viewed by 2070

Abstract

Although it was known that obesity is an independent risk factor for metabolic disorders including diabetes, the factors that link these diseases were obscure. The Hedgehog-interacting protein (Hhip) is a negative regulator in tissue remodeling, and inhibits the proliferation of adipocytes, and promotes their differentiation. In addition, Hhip was positively associated with diabetes. However, the relationship between Hhip and obesity in the human body remains unclear. An analysis of the relationship between Hhip and normal weight, overweight, and obesity levels. Participants receiving a physical checkup were recruited. Anthropometric and biochemical data were collected. Serum Hhip levels were determined by enzyme-linked immunosorbent assay (ELISA). Subjects were classified into normal-weight, overweight, and obese groups based on their body mass index (BMI). The association between Hhip and obesity was examined by multivariate linear regression analysis. In total, 294 subjects who were either of a normal weight (n = 166), overweight (n = 90), or obese (n = 38) were enrolled. Hhip concentrations were 6.51 ± 4.86 ng/mL, 5.79 ± 4.33 ng/mL, and 3.97 ± 3.4 ng/mL in normal-weight, overweight, and obese groups, respectively (p for trend = 0.032). Moreover, the regression analysis showed that BMI (β = −0.144, 95% confidence interval (CI) = −0.397−0.046, p = 0.013) was negatively associated with Hhip concentrations after adjusting for sex and age. Being overweight (β = −0.181, 95% CI = −3.311−0.400, p = 0.013) and obese (β = −0.311, 95% CI = −6.393−2.384, p < 0.001) were independently associated with Hhip concentrations after adjusting for sex, age, fasting plasma glucose, the insulin level, and other cardiometabolic risk factors. Our results showed that overweight and obese subjects had lower Hhip concentrations than those of normal weight. Being overweight and obese were negatively associated with Hhip concentrations. Hhip might be a link between obesity and diabetes. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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Review

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30 pages, 1789 KiB

Open AccessReview

The Role of Extracellular Matrix Proteins in Breast Cancer

by Arkadiusz Lepucki, Kinga Orlińska, Aleksandra Mielczarek-Palacz, Jacek Kabut, Pawel Olczyk and Katarzyna Komosińska-Vassev

J. Clin. Med. 2022, 11(5), 1250; https://doi.org/10.3390/jcm11051250 - 25 Feb 2022

Cited by 37 | Viewed by 7345

Abstract

The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell–cell and cell–matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors’ action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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15 pages, 1629 KiB

Open AccessReview

The Role of Innate and Adaptive Immune Cells in the Pathogenesis and Development of the Inflammatory Response in Ulcerative Colitis

by Aleksandra Kałużna, Paweł Olczyk and Katarzyna Komosińska-Vassev

J. Clin. Med. 2022, 11(2), 400; https://doi.org/10.3390/jcm11020400 - 13 Jan 2022

Cited by 88 | Viewed by 12115

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive immune cells play a crucial role in the pathogenesis of UC. In the case of innate immune response cells, neutrophils, dendritic cells, macrophages have a crucial impact on the development of the disease, as well as innate lymphoid cells, which have received a particular attention in recent years. On the other hand, mechanisms of the adaptive immune response involve cells such as: cytotoxic lymphocytes, regulatory lymphocytes Treg, or helper lymphocytes Th–Th2, Th9, Th17, Th22, among which significant discoveries about Th9 and Th17 lymphocytes have been made in recent years. Due to the presence of antibodies directed against resident microbiota or one’s own tissues, the influence of B lymphocytes on the development of UC is also highlighted. Additionally, the impact of cytokines on shaping the immune response as well as sustaining inflammation seems to be crucial. This review briefly describes the current state of knowledge about the involvement of the innate and adaptive immune systems in the pathogenesis of UC. The review is based on personal selection of literature that were retrieved by a selective search in PubMed using the terms “ulcerative colitis” and “pathogenesis of ulcerative colitis”. It included systematic reviews, meta-analyses and clinical trials. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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14 pages, 9269 KiB

Open AccessReview

The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases

by Alicja Derkacz, Paweł Olczyk, Krystyna Olczyk and Katarzyna Komosinska-Vassev

J. Clin. Med. 2021, 10(5), 1122; https://doi.org/10.3390/jcm10051122 - 8 Mar 2021

Cited by 49 | Viewed by 4973

Abstract

The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD). The increased activity of proteases, especially matrix metalloproteinases (MMPs), leads to excessive degradation of the extracellular matrix and the release of protein and glycoprotein fragments, previously joined with the extracellular matrix, into the circulation. MMPs participate in regulating the functions of the epithelial barrier, the immunological response, and the process of wound healing or intestinal fibrosis. At a later stage of fibrosis during IBD, excessive formation and deposition of the matrix is observed. To assess changes in the extracellular matrix, quantitative measurement of the concentration in the blood of markers dependent on the activity of proteases, involved in the breakdown of extracellular matrix proteins as well as markers indicating the formation of a new ECM, has recently been proposed. This paper describes attempts to use the quantification of ECM components as markers to predict intestinal fibrosis and evaluate the healing process of the gut. The markers which reflect increased ECM degradation, together with the ones which show the process of creating a new matrix during IBD, allow the attainment of important information regarding the changes in the intestinal tissue, epithelial integrity and extracellular matrix remodeling. This paper contains evidence confirming that ECM remodeling is an integral part of directional cell signaling in the progression of IBD, and not only a basis for the ongoing processes. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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24 pages, 754 KiB

Open AccessReview

Pharmacogenomics, How to Deal with Different Types of Variants in Next Generation Sequencing Data in the Personalized Medicine Area

by Alireza Tafazoli, Natalia Wawrusiewicz-Kurylonek, Renata Posmyk and Wojciech Miltyk

J. Clin. Med. 2021, 10(1), 34; https://doi.org/10.3390/jcm10010034 - 24 Dec 2020

Cited by 5 | Viewed by 4174

Abstract

Pharmacogenomics (PGx) is the knowledge of diverse drug responses and effects in people, based on their genomic profiles. Such information is considered as one of the main directions to reach personalized medicine in future clinical practices. Since the start of applying next generation sequencing (NGS) methods in drug related clinical investigations, many common medicines found their genetic data for the related metabolizing/shipping proteins in the human body. Yet, the employing of technology is accompanied by big obtained data, which most of them have no clear guidelines for consideration in routine treatment decisions for patients. This review article talks about different types of NGS derived PGx variants in clinical studies and try to display the current and newly developed approaches to deal with pharmacogenetic data with/without clear guidelines for considering in clinical settings. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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14 pages, 952 KiB

Open AccessSystematic Review

Pharmacogenomic Biomarkers of Follicle-Stimulating Hormone Receptor Malfunction in Females with Impaired Ovarian Response—A Genetic Survey

by Alireza Tafazoli, Sławomir Wołczyński, Natalia Wawrusiewicz-Kurylonek, Seyed-Alireza Esmaeili and Wojciech Miltyk

J. Clin. Med. 2021, 10(2), 170; https://doi.org/10.3390/jcm10020170 - 6 Jan 2021

Cited by 4 | Viewed by 3563

Abstract

Follicle-stimulating hormone receptor (FSHR) plays an essential role as one of the most important molecules in response to some of infertility related medications. Impaired ovarian reserve and poor response to such treatments are partially dependent on the FSHR molecule itself. However, the function and drug sensitivity for this receptor may change due to various allele and polymorphisms in the FSHR gene. Studies indicated some of the FSHR-mediated treatments utilized in clinical centers display different outcomes in specific populations, which may arise from FSHR altered genotypes in certain patients. To support the increased demands for reaching the personalized drug and hormone therapy in clinics, focusing on actionable variants through Pharmacogenomic analysis of this receptor may be necessary. The current study tries to display a perspective view on genetic assessments for Pharmacogenomic profiling of the FSHR gene via providing a systematic and critical overview on the genetics of FSHR and its diverse responses to ligands for infertility treatment in females with impaired ovarian responses and show the potential effects of the patient genetic make-up on related binding substances efficacy. All identified functional drug-related alleles were selected through a comprehensive literature search and analyzed. Advanced technologies for the genetic evaluation of them are also discussed properly. Full article

(This article belongs to the Special Issue Biomarkers for Diagnosis, Complications and Therapy Effects in Civilization Diseases Management)

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