Journal Description
Biomedicines
Biomedicines
is an international, peer-reviewed, open access journal on biomedicines published monthly online by MDPI. The Society for Regenerative Medicine (Russian Federation) (RPO) is affiliated with Biomedicines and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q2 (Medicine (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.4 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for Biomedicines include: IJTM, BioMed, Anesthesia Research and Emergency Care and Medicine.
Impact Factor:
4.7 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Relationship of Hematological Profiles with the Serum Complement System in Patients with Systemic Lupus Erythematosus
Biomedicines 2024, 12(5), 967; https://doi.org/10.3390/biomedicines12050967 (registering DOI) - 27 Apr 2024
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system,
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.
Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))
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Open AccessArticle
The Effects of the Coating and Aging of Biodegradable Polylactic Acid Membranes on In Vitro Primary Human Retinal Pigment Epithelium Cells
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Georgina Faura, Hana Studenovska, David Sekac, Zdenka Ellederova, Goran Petrovski and Lars Eide
Biomedicines 2024, 12(5), 966; https://doi.org/10.3390/biomedicines12050966 (registering DOI) - 26 Apr 2024
Abstract
Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative
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Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes.
Full article
(This article belongs to the Topic Advanced Functional Materials for Regenerative Medicine)
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Open AccessArticle
Superior Rectal Artery Preservation in Laparoscopically Assisted Subtotal Colectomy and Ileorectal Anastomosis for Slow-Transit Constipation
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Ta-Wei Pu, Yu-Hong Liu, Jung-Cheng Kang, Je-Ming Hu and Chao-Yang Chen
Biomedicines 2024, 12(5), 965; https://doi.org/10.3390/biomedicines12050965 (registering DOI) - 26 Apr 2024
Abstract
Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the
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Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the sample size to detect the differences in the postoperative complications and surgical and functional outcomes between patients who underwent laparoscopically assisted subtotal colectomy with and without SRA preservation. We conducted a retrospective single-center analysis of patients with STC who underwent laparoscopically assisted subtotal colectomy between 2016 and 2020. The diagnosis of STC was based on the colonic transit and anal functional tests and barium enema to exclude secondary causes. Patients were divided into group A, which underwent surgery with SRA preservation, and group B, which underwent ligation of the SRA during surgery. Outcome assessments for both groups included the incidence of anastomotic breakdown, intraoperative complications, length of hospital stay, estimated blood loss, time to first flatus, and complications. Propensity score matching allocated 34 patients to groups A and B each. Postoperative bowel function, including time to first flatus, stool, and oral intake, recovered better in group A than in group B. Anastomotic leakage, a significant postoperative complication, was less frequent in patients with SRA preservation. In conclusion, preservation of the SRA in patients undergoing laparoscopically assisted subtotal colectomy with ileorectal anastomosis for STC is associated with favorable postoperative bowel function recovery and lower anastomotic leakage rates.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessArticle
Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis
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Tomas Weitoft, Johan Rönnelid, Anders Lind, Charlotte de Vries, Anders Larsson, Barbara Potempa, Jan Potempa, Alf Kastbom, Klara Martinsson, Karin Lundberg and Marieann Högman
Biomedicines 2024, 12(5), 964; https://doi.org/10.3390/biomedicines12050964 (registering DOI) - 26 Apr 2024
Abstract
Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A
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Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman–Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho −0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho −0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho −0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho −0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.
Full article
(This article belongs to the Special Issue Role of NO in Disease: Good, Bad or Ugly)
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Open AccessArticle
Platelet-Rich Plasma Injections in Chronic Lateral Ankle Instability: A Case Series
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Ivan Medina-Porqueres, Pablo Martin-Garcia, Sofia Sanz-De-Diego, Marcelo Reyes-Eldblom, Francisco Moya-Torrecilla, Rafael Mondragon-Cortes, Daniel Rosado-Velazquez and Abel Gomez-Caceres
Biomedicines 2024, 12(5), 963; https://doi.org/10.3390/biomedicines12050963 (registering DOI) - 26 Apr 2024
Abstract
The platelet-rich plasma (PRP) approach may be an effective treatment for joint and cartilage pathologies. However, the rationale for its effectiveness on joint instability is limited. This study aimed to assess the safety and effectiveness of PRP injections in patients with chronic lateral
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The platelet-rich plasma (PRP) approach may be an effective treatment for joint and cartilage pathologies. However, the rationale for its effectiveness on joint instability is limited. This study aimed to assess the safety and effectiveness of PRP injections in patients with chronic lateral ankle instability (CLAI). This retrospective study was performed at a single-center outpatient clinic between January 2015 and February 2023 and included pre-intervention assessment and short-term follow-up. Patients were excluded if they had received previous surgical treatment or had constitutional hyperlaxity, systemic diseases, or grade II or III osteoarthritis. The clinical and functional evaluation consisted of the Karlsson score, the Cumberland Ankle Instability Tool (CAIT), Good’s grading system, the patient’s subjective satisfaction level, and the time required to return to exercise. The entire PRP therapy regime consisted of three PRP administrations at 7-day intervals and follow-up appointments. PRP was administered both intraarticularly and into talofibular ligaments. A total of 47 consecutive patients with CLAI were included, 11 were female (23.4%), with a mean age at intervention of 31.19 ± 9.74 years. A statistically significant improvement was found in the CAIT and Karlsson scores at 3 months (27.74 ± 1.68 and 96.45 ± 4.28, respectively) relative to the pre-intervention status (10.26 ± 4.33 and 42.26 ± 14.9, respectively, p < 0.000). The mean follow-up of patients with CLAI was 17.94 ± 3.25 weeks. This study represents successful short-term functional and clinical outcomes in patients with CLAI after PRP treatment, with no adverse effects. It demonstrates the feasibility of a randomized controlled trial to further assess this therapy.
Full article
(This article belongs to the Special Issue Musculoskeletal Regenerative Medicine)
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Open AccessArticle
Expression of Selected miRNAs in Undifferentiated Carcinoma with Osteoclast-like Giant Cells (UCOGC) of the Pancreas: Comparison with Poorly Differentiated Pancreatic Ductal Adenocarcinoma
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Alexey Popov, Jan Hrudka, Arpád Szabó, Martin Oliverius, Zdeněk Šubrt, Jana Vránová, Vanda Ciprová, Jana Moravcová and Václav Mandys
Biomedicines 2024, 12(5), 962; https://doi.org/10.3390/biomedicines12050962 (registering DOI) - 26 Apr 2024
Abstract
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal
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Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs.
Full article
(This article belongs to the Special Issue Pancreatic, Liver, Biliary Tract and Intestinal Diseases: Pathogenesis, Diagnostics and Therapy)
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Open AccessReview
The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy
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Piotr Wańczura, David Aebisher, Mateusz A. Iwański, Angelika Myśliwiec, Klaudia Dynarowicz and Dorota Bartusik-Aebisher
Biomedicines 2024, 12(5), 961; https://doi.org/10.3390/biomedicines12050961 (registering DOI) - 26 Apr 2024
Abstract
Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to
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Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to block cholesterol synthesis. Many times, additional drugs are also used with this method to lower lipid concentrations in order to achieve certain values of low-density lipoprotein (LDL) cholesterol. Recent advances in photodynamic therapy (PDT) as a new cancer treatment have gained the therapy much attention as a minimally invasive and highly selective method. Photodynamic therapy has been proven more effective than chemotherapy, radiotherapy, and immunotherapy alone in numerous studies. Consequently, photodynamic therapy research has expanded in many fields of medicine due to its increased therapeutic effects and reduced side effects. Currently, PDT is the most commonly used therapy for treating age-related macular degeneration, as well as inflammatory diseases, and skin infections. The effectiveness of photodynamic therapy against a number of pathogens has also been demonstrated in various studies. Also, PDT has been used in the treatment of cardiovascular diseases, such as atherosclerosis and hyperplasia of the arterial intima. This review evaluates the effectiveness and usefulness of photodynamic therapy in cardiovascular diseases. According to the analysis, photodynamic therapy is a promising approach for treating cardiovascular diseases and may lead to new clinical trials and management standards. Our review addresses the used therapeutic strategies and also describes new therapeutic strategies to reduce the cardiovascular burden that is induced by lipids.
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(This article belongs to the Section Molecular and Translational Medicine)
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Evaluation of Clinical Remission in Best-Performing Severe Asthmatic Patients Treated for Three Years with Mepolizumab
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Diego Bagnasco, Benedetta Bondi, Marco Caminati, Stefania Nicola, Laura Pini, Manlio Milanese, Luisa Brussino, Gianenrico Senna, Giorgio Walter Canonica and Fulvio Braido
Biomedicines 2024, 12(5), 960; https://doi.org/10.3390/biomedicines12050960 (registering DOI) - 26 Apr 2024
Abstract
Background: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its
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Background: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. Objective: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. Methods: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. Results: According to the criteria, 39–52% of patients experienced complete remission in the first year, increasing to 51–73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Conclusions: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.
Full article
(This article belongs to the Special Issue Recent Advances in Chronic Rhinosinusitis and Asthma)
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Open AccessSystematic Review
Porous Tantalum Acetabular Cups in Primary and Revision Total Hip Arthroplasty: What Has Been the Experience So Far?—A Systematic Literature Review
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Evangelia Argyropoulou, Evangelos Sakellariou, Athanasios Galanis, Panagiotis Karampinas, Meletis Rozis, Konstantinos Koutas, George Tsalimas, Elias Vasiliadis, John Vlamis and Spiros Pneumaticos
Biomedicines 2024, 12(5), 959; https://doi.org/10.3390/biomedicines12050959 (registering DOI) - 25 Apr 2024
Abstract
Background: The global population, especially in the Western world, is constantly aging and the need for total hip arthroplasties has rocketed, hence there has been a notable increase in revision total hip arthroplasty cases. As time has passed, a considerable developments in science
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Background: The global population, especially in the Western world, is constantly aging and the need for total hip arthroplasties has rocketed, hence there has been a notable increase in revision total hip arthroplasty cases. As time has passed, a considerable developments in science and medicine have been attained which have also resulted in the evolution of both surgical techniques and implants. Continuous improvements have allowed large bore bearings to be utilized which provide an increased range of motion, with ameliorated stability and a very low rate of wear. The trend for almost the last two decades has been the employment of porous tantalum acetabular cups. Several studies exist comparing them with other conventional methods for total hip arthroplasties, exhibiting promising short and midterm results. Methods: The Preferred Reporting Items for Systematic Reviews and a Meta-Analysis (PRISMA) were used to identify published studies in a comprehensive search up to February 2023, and these studies were reviewed by the authors of the article. Specific rigorous pre-determined inclusion and exclusion criteria were implemented. Results: Fifty-one studies met our inclusion criteria and were involved in the systematic review. Sixteen studies examined postoperative clinical and radiological outcomes of using a tantalum cup in primary and revision total hip arthroplasty, whilst four biomechanical studies proved the superiority of tantalum acetabular components. Five articles provided a thorough comparison between tantalum and titanium acetabular cups, while the other studies analyzed long-terms results and complication rates. Conclusions: Porous tantalum acetabular cups appear to be a valuable option in revision total hip arthroplasty, providing clinical improvement, radiological stability, and promising long-term outcomes. However, ongoing research, longer follow-up periods, and careful consideration of patient factors are essential to further validate and refine the use of tantalum in various clinical scenarios.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
Open AccessArticle
Potential Role of Circulating PD-L1+ Leukocytes as a Predictor of Response to Anti-PD-(L)1 Therapy in NSCLC Patients
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Georgia Anguera, Maria Mulet, Carlos Zamora, Rubén Osuna-Gómez, Andrés Barba, Ivana Sullivan, Jorgina Serra-López, Elisabet Cantó, Silvia Vidal and Margarita Majem
Biomedicines 2024, 12(5), 958; https://doi.org/10.3390/biomedicines12050958 (registering DOI) - 25 Apr 2024
Abstract
PD-(L)1 inhibitors are part of the treatment strategy for non-small cell lung cancer (NSCLC) although its efficacy is limited to certain patients. Our study aimed to identify patients who might benefit from anti-PD-(L)1 inhibitors by analyzing the PD-L1 expression on circulating leukocytes and
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PD-(L)1 inhibitors are part of the treatment strategy for non-small cell lung cancer (NSCLC) although its efficacy is limited to certain patients. Our study aimed to identify patients who might benefit from anti-PD-(L)1 inhibitors by analyzing the PD-L1 expression on circulating leukocytes and its evolution during treatment. One hundred thirteen NSCLC patients, according to their radiological response after 10–12 weeks of treatment, were classified into responders, stable, and progressive disease. Percentages of circulating PD-L1+ leukocytes, PD-L1+ platelets (PLTs), and leukocyte-PLT complexes were assessed using flow cytometry, and plasma concentrations of soluble immunomodulatory factors were quantified by ELISA. Responders exhibited significantly higher pre-treatment percentages of PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs than progressors. The percentages of these populations decreased in responders post-treatment, contrasting with stables and progressors. PLTs notably contributed to PD-L1 expression in CD14+ cells and neutrophils. Plasma cytokine analysis revealed baseline differences only in IL-17 concentration among groups, whereas network analyses highlighted distinct association patterns between plasma molecules and PD-L1+ leukocytes after 10–12 weeks of treatment. Our findings suggest that pre-treatment assessment of circulating PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs may be helpful in identifying NSCLC patients who are potential candidates for anti-PD-(L)1 therapy.
Full article
(This article belongs to the Special Issue PD-1/PD-L1 and Immunotherapy)
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Open AccessArticle
Frequency of Androgen Receptor Positivity in Tumors: A Study Evaluating More Than 18,000 Tumors
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Florian Viehweger, Jennifer Hoop, Lisa-Marie Tinger, Christian Bernreuther, Franziska Büscheck, Till S. Clauditz, Andrea Hinsch, Frank Jacobsen, Andreas M. Luebke, Stefan Steurer, Claudia Hube-Magg, Martina Kluth, Andreas H. Marx, Till Krech, Patrick Lebok, Christoph Fraune, Eike Burandt, Guido Sauter, Ronald Simon and Sarah Minner
Biomedicines 2024, 12(5), 957; https://doi.org/10.3390/biomedicines12050957 (registering DOI) - 25 Apr 2024
Abstract
Androgen receptor (AR) is a transcription factor expressed in various normal tissues and is a therapeutic target for prostate and possibly other cancers. A TMA containing 18,234 samples from 141 different tumor types/subtypes and 608 samples of 76 different normal tissue types was
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Androgen receptor (AR) is a transcription factor expressed in various normal tissues and is a therapeutic target for prostate and possibly other cancers. A TMA containing 18,234 samples from 141 different tumor types/subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. AR positivity was found in 116 tumor types including 66 tumor types (46.8%) with ≥1 strongly positive tumor. Moderate/strong AR positivity was detected in testicular sex cord-stromal tumors (93.3–100%) and neoplasms of the prostate (79.3–98.7%), breast (25.0–75.5%), other gynecological tumors (0.9–100%), kidney (5.0–44.1%), and urinary bladder (5.4–24.2%). Low AR staining was associated with advanced tumor stage (pTa versus pT2-4; p < 0.0001) in urothelial carcinoma; advanced pT (p < 0.0001), high tumor grade (p < 0.0001), nodal metastasis (p < 0.0001), and reduced survival (p = 0.0024) in invasive breast carcinoma; high pT (p < 0.0001) and grade (p < 0.0001) in clear cell renal cell carcinoma (RCC); and high pT (p = 0.0055) as well as high grade (p < 0.05) in papillary RCC. AR staining was unrelated to histopathological/clinical features in 157 endometrial carcinomas and in 221 ovarian carcinomas. Our data suggest a limited role of AR immunohistochemistry for tumor distinction and a prognostic role in breast and clear cell RCC and highlight tumor entities that might benefit from AR-targeted therapy.
Full article
(This article belongs to the Section Cancer Biology and Oncology)
Open AccessArticle
Effects of Deuterium Depletion on Age-Declining Thymopoiesis In Vivo
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Nataliya V. Yaglova, Sergey S. Obernikhin, Ekaterina P. Timokhina, Dibakhan A. Tsomartova, Valentin V. Yaglov, Svetlana V. Nazimova, Elina S. Tsomartova, Marina Y. Ivanova, Elizaveta V. Chereshneva and Tatiana A. Lomanovskaya
Biomedicines 2024, 12(5), 956; https://doi.org/10.3390/biomedicines12050956 (registering DOI) - 25 Apr 2024
Abstract
The thymus provides maturation and migration of T cells to peripheral organs of immunity, where they recognize diverse antigens and maintain immunological memory and self-tolerance. The thymus is known to be involved with age and in response to stress factors. Therefore, the search
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The thymus provides maturation and migration of T cells to peripheral organs of immunity, where they recognize diverse antigens and maintain immunological memory and self-tolerance. The thymus is known to be involved with age and in response to stress factors. Therefore, the search for approaches to the restoration of thymopoiesis is of great interest. The present investigation was aimed at evaluating how prolonged deuterium depletion affects morphogenetic processes and the physiological transition of the thymus to age-related involution. The study was performed on 60 male Wistar rats subjected to consumption of deuterium-depleted water with a 10 ppm deuterium content for 28 days. The control rats consumed distilled water with a normal deuterium content of 150 ppm. The examination found no significant differences in body weight gain or the amount of water consumed. The exposed rats exhibited similar to control dynamics of the thymus weight but significant changes in thymic cell maturation according to cytofluorimetric analysis of thymic subpopulations. Changes in T cell production were not monotonic and differentially engaged morphogenetic processes of cell proliferation, differentiation, and migration. The reactive response to deuterium depletion was a sharp increase in the number of progenitor CD4−CD8− cells and their differentiation into T cells. The compensatory reaction was inhibition of thymopoiesis with more pronounced suppression of differentiation of T-cytotoxic lymphocytes, followed by intensification of emigration of mature T cells to the bloodstream. This period lasts from 3 to 14 days, then differentiation of thymic lymphocytes is restored, later cell proliferation is activated, and finally the thymopoiesis rate exceeds the control values. The increase in the number of thymic progenitor cells after 3–4 weeks suggests consideration of deuterium elimination as a novel approach to prevent thymus involution.
Full article
(This article belongs to the Special Issue Deuterium Depletion: From Basic Research to Novel Therapeutic Approaches)
Open AccessArticle
Exploring Motor Network Connectivity in State-Dependent Transcranial Magnetic Stimulation: A Proof-of-Concept Study
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Laura Marzetti, Alessio Basti, Roberto Guidotti, Antonello Baldassarre, Johanna Metsomaa, Christoph Zrenner, Antea D’Andrea, Saeed Makkinayeri, Giulia Pieramico, Risto J. Ilmoniemi, Ulf Ziemann, Gian Luca Romani and Vittorio Pizzella
Biomedicines 2024, 12(5), 955; https://doi.org/10.3390/biomedicines12050955 (registering DOI) - 25 Apr 2024
Abstract
State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This
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State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the Motor Network (MN) and how the MN state affects responses to the transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to the left M1 in eight subjects at rest, with simultaneous EEG. Motor-evoked potentials (MEPs) were measured from the right hand. The source space functional connectivity of the left M1 to the whole brain was assessed using the imaginary part of the phase locking value at the frequency of the sensorimotor μ-rhythm in a 1 s window before the pulse. Group-level connectivity revealed functional links between the left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At the single-subject level, this relation is more highly expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity-based NIBS.
Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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Open AccessArticle
Decreased IL-1 β Secretion as a Potential Predictor of Tuberculosis Recurrence in Individuals Diagnosed with HIV
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Marina Nosik, Konstantin Ryzhov, Asya V. Kudryavtseva, Ulyana Kuimova, Alexey Kravtchenko, Alexandr Sobkin, Vitaly Zverev and Oxana Svitich
Biomedicines 2024, 12(5), 954; https://doi.org/10.3390/biomedicines12050954 (registering DOI) - 25 Apr 2024
Abstract
Background: The mechanisms of the formation of immunological competence against tuberculosis (TB), and especially those associated with HIV co-infection, remain poorly understood. However, there is an urgent need for risk recurrence predictive biomarkers, as well as for predictors of successful treatment outcomes. The
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Background: The mechanisms of the formation of immunological competence against tuberculosis (TB), and especially those associated with HIV co-infection, remain poorly understood. However, there is an urgent need for risk recurrence predictive biomarkers, as well as for predictors of successful treatment outcomes. The goal of the study was to identify possible immunological markers of TB recurrence in individuals with HIV/TB co-infection. Methods: The plasma levels of IFN-γ, TNF-α, IL-10, and IL-1β (cytokines which play important roles in the immune activation and protection against Mycobacterium tuberculosis) were measured using ELISA EIA-BEST kits. The cytokine concentrations were determined using a standard curve obtained with the standards provided by the manufacturer of each kit. Results: A total of 211 individuals were enrolled in the study as follows: 62 patients with HIV/TB co-infection, 52 with HIV monoinfection, 52 with TB monoinfection, and 45 healthy donors. Out of the 62 patients with HIV/TB, 75.8% (47) of patients were newly diagnosed with HIV and TB, and 24.2% (15) displayed recurrent TB and were newly diagnosed with HIV. Decreased levels of IFN-γ, TNF-α, and IL-10 were observed in patients with HIV/TB when compared with HIV and TB patients. However, there was no difference in IFN-γ, TNF-α, or IL-10 secretion between both HIV/TB groups. At the same time, an almost 4-fold decrease in Il-1β levels was detected in the HIV/TB group with TB recurrence when compared with the HIV/TB group (p = 0.0001); a 2.8-fold decrease when compared with HIV patients (p = 0.001); and a 2.2-fold decrease with newly diagnosed TB patients (p = 0.001). Conclusions: Significantly decreased Il-1β levels in HIV/TB patients’ cohort with secondary TB indicate that this cytokine can be a potential biomarker of TB recurrence.
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(This article belongs to the Special Issue Cytokines as Biomarkers for Diagnosis and Treatment of Chronic Inflammatory Conditions: Concerns, Pitfalls, Boundaries and Future Perspectives)
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Safety Profile of the Trastuzumab-Based ADCs: Analysis of Real-World Data Registered in EudraVigilance
by
Claudiu Morgovan, Carmen Maximiliana Dobrea, Anca Butuca, Anca Maria Arseniu, Adina Frum, Luca Liviu Rus, Adriana Aurelia Chis, Anca Maria Juncan, Felicia Gabriela Gligor, Cecilia Georgescu, Steliana Ghibu and Andreea Loredana Vonica-Tincu
Biomedicines 2024, 12(5), 953; https://doi.org/10.3390/biomedicines12050953 (registering DOI) - 25 Apr 2024
Abstract
Trastuzumab (T) and tyrosine kinase inhibitors (TKIs) are among the first-line treatments recommended for HER2-positive breast cancer. More recently, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) have been authorized, and they represent the second-line therapy in this type
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Trastuzumab (T) and tyrosine kinase inhibitors (TKIs) are among the first-line treatments recommended for HER2-positive breast cancer. More recently, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) have been authorized, and they represent the second-line therapy in this type of cancer. The present study aimed to evaluate adverse drug reactions (ADRs) associated with T-based ADCs that were spontaneously reported in EudraVigilance—the European pharmacovigilance database. Out of 42,272 ADRs reported for currently approved ADCs on the market, 24% of ADRs were related to T-DM1, while 12% of ADRs were related to T-DXd. T-DM1 had a higher probability of reporting eye, ear and labyrinth, and cardiac and hepatobiliary ADRs, while T-DXd had a higher probability of reporting respiratory, thoracic and mediastinal, blood and lymphatic system, metabolism and nutrition, and gastrointestinal ADRs. The present research found that in terms of hematological disorders, T-DM1 and T-DXd had a higher probability of reporting ADRs than TKIs. Moreover, the data showed that T-DM1 seemed to have a higher risk of cardiotoxicity than T-DXd, while T-DXd had a higher probability of reporting metabolism and nutrition disorders than T-DM1.
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(This article belongs to the Special Issue State-of-the-Art Drug Delivery in Europe)
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Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review
by
Hiroki Kurumi, Yoshihiro Yokoyama, Takehiro Hirano, Kotaro Akita, Yuki Hayashi, Tomoe Kazama, Hajime Isomoto and Hiroshi Nakase
Biomedicines 2024, 12(5), 952; https://doi.org/10.3390/biomedicines12050952 (registering DOI) - 25 Apr 2024
Abstract
Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood,
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Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood, abnormalities of the cytokine profiles are deeply involved in its pathophysiology. Therefore, an approach focused on the cytokine profile of individual patients with UC is ideal. Recent studies have demonstrated that molecular analysis of cytokine profiles in UC can predict response to each advanced therapy. This narrative review summarizes the molecules involved in the efficacy of various advanced therapies for UC. Understanding these associations may be helpful in selecting optimal therapeutic agents.
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(This article belongs to the Special Issue Molecular Biomarkers in Inflammatory Bowel Disease: Pathophysiology and New Therapeutic Strategies)
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The Congestion “Pandemic” in Acute Heart Failure Patients
by
Daniela Mocan, Radu Ioan Lala, Maria Puschita, Luminita Pilat, Dan Alexandru Darabantiu and Adina Pop-Moldovan
Biomedicines 2024, 12(5), 951; https://doi.org/10.3390/biomedicines12050951 (registering DOI) - 24 Apr 2024
Abstract
Congestion not only represents a cardinal sign of heart failure (HF) but is also now recognized as the primary cause of hospital admissions, rehospitalization, and mortality among patients with acute heart failure (AHF). Congestion can manifest through various HF phenotypes in acute settings:
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Congestion not only represents a cardinal sign of heart failure (HF) but is also now recognized as the primary cause of hospital admissions, rehospitalization, and mortality among patients with acute heart failure (AHF). Congestion can manifest through various HF phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Among patients with AHF, achieving complete decongestion is challenging, as more than half still experience residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with AHF by highlighting insights into the pathophysiological mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion.
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(This article belongs to the Section Molecular and Translational Medicine)
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Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome
by
Madalina Boruga, Susa Septimiu-Radu, Prashant Sunil Nandarge, Ahmed Elagez, Gabriela Doros, Voichita Elena Lazureanu, Emil Robert Stoicescu, Elena Tanase, Roxana Iacob, Andreea Dumitrescu, Adrian Vasile Bota, Coralia Cotoraci and Melania Lavinia Bratu
Biomedicines 2024, 12(5), 950; https://doi.org/10.3390/biomedicines12050950 (registering DOI) - 24 Apr 2024
Abstract
The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in
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The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the “Victor Babes” Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.
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(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—2nd Edition)
Open AccessArticle
Angiopoietin-2 and Angiopoietin-like Proteins with a Prospective Role in Predicting Diabetic Nephropathy
by
Eman Alshawaf, Mohamed Abu-Farha, Anwar Mohammad, Sriraman Devarajan, Irina Al-Khairi, Preethi Cherian, Hamad Ali, Hawra Al-Matrouk, Fahd Al-Mulla, Abdulnabi Al Attar and Jehad Abubaker
Biomedicines 2024, 12(5), 949; https://doi.org/10.3390/biomedicines12050949 (registering DOI) - 24 Apr 2024
Abstract
Angiopoietins are crucial growth factors for maintaining a healthy, functional endothelium. Patients with type 2 diabetes (T2D) exhibit significant levels of angiogenic markers, particularly Angiopoietin-2, which compromises endothelial integrity and is connected to symptoms of endothelial injury and failure. This report examines the
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Angiopoietins are crucial growth factors for maintaining a healthy, functional endothelium. Patients with type 2 diabetes (T2D) exhibit significant levels of angiogenic markers, particularly Angiopoietin-2, which compromises endothelial integrity and is connected to symptoms of endothelial injury and failure. This report examines the levels of circulating angiopoietins in people with T2D and diabetic nephropathy (DN) and explores its link with ANGPTL proteins. We quantified circulating ANGPTL3, ANGPTL4, ANGPTL8, Ang1, and Ang2 in the fasting plasma of 117 Kuwaiti participants, of which 50 had T2D and 67 participants had DN. The Ang2 levels increased with DN (4.34 ± 0.32 ng/mL) compared with T2D (3.42 ± 0.29 ng/mL). This increase correlated with clinical parameters including the albumin-to-creatinine ratio (ACR) (r = 0.244, p = 0.047), eGFR (r = −0.282, p = 0.021), and SBP (r = −0.28, p = 0.024). Furthermore, Ang2 correlated positively to both ANGPTL4 (r = 0.541, p < 0.001) and ANGPTL8 (r = 0.41, p = 0.001). Multiple regression analysis presented elevated ANGPTL8 and ACRs as predictors for Ang2’s increase in people with DN. In people with T2D, ANGPTL4 positively predicted an Ang2 increase. The area under the curve (AUC) in receiver operating characteristic (ROC) analysis of the combination of Ang2 and ANGPTL8 was 0.77 with 80.7% specificity. In conclusion, significantly elevated Ang2 in people with DN correlated with clinical markers such as the ACR, eGFR, and SBP, ANGPTL4, and ANGPTL8 levels. Collectively, this study highlights a close association between Ang2 and ANGPTL8 in a population with DN, suggesting them as DN risk predictors.
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(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches in Diabetic Microvascular Complications)
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CFH (rs1061170, rs1410996), KDR (rs2071559, rs1870377) and KDR and CFH Serum Levels in AMD Development and Treatment Efficacy
by
Dzastina Cebatoriene, Alvita Vilkeviciute, Greta Gedvilaite, Akvile Bruzaite, Loresa Kriauciuniene, Dalia Zaliuniene and Rasa Liutkeviciene
Biomedicines 2024, 12(5), 948; https://doi.org/10.3390/biomedicines12050948 (registering DOI) - 24 Apr 2024
Abstract
Background: Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Av-vascular endothelial growth factor (anti-VEGF) therapies have been shown to be effective, but they do not
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Background: Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Av-vascular endothelial growth factor (anti-VEGF) therapies have been shown to be effective, but they do not respond optimally to all patients. Objective. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the CFH (rs1061170, rs1410996) and KDR (rs2071559, rs1870377) genes and the association of CFH and KDR serum levels in patients with AMD. Results. A cohort of 255 patients with early AMD, 252 patients with exudative AMD, and 349 healthy controls underwent genotyping analysis, which revealed significant associations between CFH polymorphisms and the risk of exudative AMD. The CFH rs1061170 CC genotype was associated with an increased risk of early AMD (p = 0.046). For exudative AMD, the CFH rs1061170 TC + CC genotype increased odds (p < 0.001), while the rs1410996 GA + AA genotype decreased odds (p < 0.001). Haplotypes of CFH SNPs were associated with decreased odds of AMD. In terms of response to treatment, none of the SNPs were associated with the response to anti-VEGF treatment. We also found that both early and exudative AMD patients had lower CFH serum levels compared to the control group (p = 0.038 and p = 0.006, respectively). Exudative AMD patients with the CT genotype of CFH rs1061170 had lower CFH serum levels compared to the control group (p = 0.035). Exudative AMD patients with the GG genotype of CFH rs1410996 also had lower CFH serum levels compared to the control group (p = 0.021). Conclusions. CFH polymorphisms influence susceptibility to AMD but do not correlate with a response to anti-VEGF therapy. Further research is imperative to fully evaluate the developmental significance, treatment efficacy, and predictive role in influencing susceptibility to anti-VEGF therapy for KDR and CFH.
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(This article belongs to the Special Issue Age-Related Macular Degeneration: Causes, Pathogenesis, Diagnosis, and Intervention)
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