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
Single and Combined Effects of Cannabigerol (CBG) and Cannabidiol (CBD) in Mouse Models of Oxaliplatin-Associated Mechanical Sensitivity, Opioid Antinociception, and Naloxone-Precipitated Opioid Withdrawal
Biomedicines 2024, 12(6), 1145; https://doi.org/10.3390/biomedicines12061145 (registering DOI) - 22 May 2024
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients, with estimates of at least 30% of patients experiencing persistent neuropathy for months or years after treatment cessation. An emerging potential intervention for the treatment of CIPN
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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients, with estimates of at least 30% of patients experiencing persistent neuropathy for months or years after treatment cessation. An emerging potential intervention for the treatment of CIPN is cannabinoid-based pharmacotherapies. We have previously demonstrated that treatment with the psychoactive CB1/CB2 cannabinoid receptor agonist Δ9-tetrahydrocannabinol (Δ9-THC) or the non-psychoactive, minor phytocannabinoid cannabidiol (CBD) can attenuate paclitaxel-induced mechanical sensitivity in a mouse model of CIPN. We then showed that the two compounds acted synergically when co-administered in the model, giving credence to the so-called entourage effect. We and others have also demonstrated that CBD can attenuate several opioid-associated behaviors. Most recently, it was reported that another minor cannabinoid, cannabigerol (CBG), attenuated cisplatin-associated mechanical sensitivity in mice. Therefore, the goals of the present set of experiments were to determine the single and combined effects of cannabigerol (CBG) and cannabidiol (CBD) in oxaliplatin-associated mechanical sensitivity, naloxone-precipitated morphine withdrawal, and acute morphine antinociception in male C57BL/6 mice. Results demonstrated that CBG reversed oxaliplatin-associated mechanical sensitivity only under select dosing conditions, and interactive effects with CBD were sub-additive or synergistic depending upon dosing conditions too. Pretreatment with a selective α2-adrenergic, CB1, or CB2 receptor selective antagonist significantly attenuated the effect of CBG. CBG and CBD decreased naloxone-precipitated jumping behavior alone and acted synergistically in combination, while CBG attenuated the acute antinociceptive effects of morphine and CBD. Taken together, CBG may have therapeutic effects like CBD as demonstrated in rodent models, and its interactive effects with opioids or other phytocannabinoids should continue to be characterized.
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(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)
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Poptosis or Peptide-Induced Transmembrane Pore Formation: A Novel Way to Kill Cancer Cells without Affecting Normal Cells
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Matthew R. Pincus, Miriam Silberstein, Nitzan Zohar, Ehsan Sarafraz-Yazdi and Wilbur B. Bowne
Biomedicines 2024, 12(6), 1144; https://doi.org/10.3390/biomedicines12061144 (registering DOI) - 22 May 2024
Abstract
Recent advances in cancer treatment like personalized chemotherapy and immunotherapy are aimed at tumors that meet certain specifications. In this review, we describe a new approach to general cancer treatment, termed peptide-induced poptosis, in which specific peptides, e.g., PNC-27 and its shorter analogue,
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Recent advances in cancer treatment like personalized chemotherapy and immunotherapy are aimed at tumors that meet certain specifications. In this review, we describe a new approach to general cancer treatment, termed peptide-induced poptosis, in which specific peptides, e.g., PNC-27 and its shorter analogue, PNC-28, that contain the segment of the p53 transactivating 12–26 domain that bind to HDM-2 in its 1–109 domain, bind to HDM-2 in the membranes of cancer cells, resulting in transmembrane pore formation and the rapid extrusion of cancer cell contents, i.e., tumor cell necrosis. These peptides cause tumor cell necrosis of a wide variety of solid tissue and hematopoietic tumors but have no effect on the viability and growth of normal cells since they express at most low levels of membrane-bound HDM-2. They have been found to successfully treat a highly metastatic pancreatic tumor as well as stem-cell-enriched human acute myelogenous leukemias in nude mice, with no evidence of off-target effects. These peptides also are cytotoxic to chemotherapy-resistant cancers and to primary tumors. We performed high-resolution scanning immuno-electron microscopy and visualized the pores in cancer cells induced by PNC-27. This peptide forms 1:1 complexes with HDM-2 in a temperature-independent step, followed by dimerization of these complexes to form transmembrane channels in a highly temperature-dependent step parallel to the mode of action of other membranolytic but less specific agents like streptolysin. These peptides therefore may be effective as general anti-cancer agents.
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(This article belongs to the Special Issue Medicinal Chemistry in Drug Design and Discovery)
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Open AccessArticle
Clinicopathological Characteristics and Disease Chronicity in Glomerular Diseases: A Decade-Long Study at Romania’s Largest Kidney Biopsy Reference Center
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Nicolae Pană, Gabriel Ștefan, Simona Stancu, Adrian Zugravu, Otilia Ciurea, Nicoleta Petre, Gabriel Mircescu and Cristina Căpușă
Biomedicines 2024, 12(6), 1143; https://doi.org/10.3390/biomedicines12061143 (registering DOI) - 22 May 2024
Abstract
Glomerular diseases (GDs), significant causes of end-stage kidney disease, are better understood through epidemiological studies based on kidney biopsies (KBs), which provide important insights into their prevalence and characteristics. This study aims to analyze the clinicopathological features of GDs diagnosed from 2008 to
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Glomerular diseases (GDs), significant causes of end-stage kidney disease, are better understood through epidemiological studies based on kidney biopsies (KBs), which provide important insights into their prevalence and characteristics. This study aims to analyze the clinicopathological features of GDs diagnosed from 2008 to 2017 at Romania’s largest reference center. In this decade-long study, 1254 adult patients diagnosed with GDs were included. The local previously validated renal histopathological prognostic score was calculated for each KB using four histopathologic lesions: global glomerulosclerosis, tubular atrophy, interstitial fibrosis and fibrocellular/fibrous crescents. The mean patient age was 50 years, with a male predominance (57%). The primary referral reasons were nephrotic syndrome (46%), nephritic syndrome (37%), chronic kidney disease (12%), asymptomatic urinary abnormalities (4%), and acute kidney injury (1%). Immunoglobulin A nephropathy (IgAN) was the most frequently diagnosed GD (20%), aligning with frequencies reported in European registries. Diabetic glomerular nephropathy was the most common secondary GD (10%). It also presented the highest median renal histopathological prognostic score (2), indicating a poorer prognosis. Lower eGFR and higher proteinuria were independently associated with higher scores. This decade-long study highlights IgAN as the most frequent GD diagnosed by KB. Diabetic glomerular nephropathy was identified as the most common secondary GD. The renal histopathological prognostic score, notably high in diabetic glomerular nephropathy patients, was correlated with lower eGFR and higher proteinuria, underlining its clinical relevance.
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(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessArticle
Simple and Fast Prediction of Gestational Diabetes Mellitus Based on Machine Learning and Near-Infrared Spectra of Serum: A Proof of Concept Study at Different Stages of Pregnancy
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Daniela Mennickent, Lucas Romero-Albornoz, Sebastián Gutiérrez-Vega, Claudio Aguayo, Federico Marini, Enrique Guzmán-Gutiérrez and Juan Araya
Biomedicines 2024, 12(6), 1142; https://doi.org/10.3390/biomedicines12061142 (registering DOI) - 21 May 2024
Abstract
Gestational diabetes mellitus (GDM) is a hyperglycemic state that is typically diagnosed by an oral glucose tolerance test (OGTT), which is unpleasant, time-consuming, has low reproducibility, and results are tardy. The machine learning (ML) predictive models that have been proposed to improve GDM
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Gestational diabetes mellitus (GDM) is a hyperglycemic state that is typically diagnosed by an oral glucose tolerance test (OGTT), which is unpleasant, time-consuming, has low reproducibility, and results are tardy. The machine learning (ML) predictive models that have been proposed to improve GDM diagnosis are usually based on instrumental methods that take hours to produce a result. Near-infrared (NIR) spectroscopy is a simple, fast, and low-cost analytical technique that has never been assessed for the prediction of GDM. This study aims to develop ML predictive models for GDM based on NIR spectroscopy, and to evaluate their potential as early detection or alternative screening tools according to their predictive power and duration of analysis. Serum samples from the first trimester (before GDM diagnosis) and the second trimester (at the time of GDM diagnosis) of pregnancy were analyzed by NIR spectroscopy. Four spectral ranges were considered, and 80 mathematical pretreatments were tested for each. NIR data-based models were built with single- and multi-block ML techniques. Every model was subjected to double cross-validation. The best models for first and second trimester achieved areas under the receiver operating characteristic curve of 0.5768 ± 0.0635 and 0.8836 ± 0.0259, respectively. This is the first study reporting NIR-spectroscopy-based methods for the prediction of GDM. The developed methods allow for prediction of GDM from 10 µL of serum in only 32 min. They are simple, fast, and have a great potential for application in clinical practice, especially as alternative screening tools to the OGTT for GDM diagnosis.
Full article
(This article belongs to the Topic Pathogenesis of Pregnancy-Related Complications 2.0)
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Biomarkers and Signaling Pathways Implicated in the Pathogenesis of Idiopathic Multicentric Castleman Disease/Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly (TAFRO) Syndrome
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Remi Sumiyoshi, Tomohiro Koga and Atsushi Kawakami
Biomedicines 2024, 12(6), 1141; https://doi.org/10.3390/biomedicines12061141 (registering DOI) - 21 May 2024
Abstract
Idiopathic multicentric Castleman disease (iMCD) and TAFRO syndrome present a variety of symptoms thought to be caused by excessive inflammatory cytokines and chemokines, but the underlying mechanisms are unknown. iMCD is broadly classified into two types: iMCD-NOS and iMCD-TAFRO, which have distinct laboratory
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Idiopathic multicentric Castleman disease (iMCD) and TAFRO syndrome present a variety of symptoms thought to be caused by excessive inflammatory cytokines and chemokines, but the underlying mechanisms are unknown. iMCD is broadly classified into two types: iMCD-NOS and iMCD-TAFRO, which have distinct laboratory findings, pathological features, and responses to treatments. It is thought that iMCD-NOS, particularly the IPL type, responds favorably to IL-6 inhibitors due to its IL-6-centric profile. iMCD-TAFRO frequently progresses acutely and seriously, similar to TAFRO syndrome. Elevated levels of cytokines, including IL-1β, TNF-α, IL-10, and IL-23, as well as chemokines like CXCL13 and CXCL-10 (especially in iMCD-TAFRO), SAA, and VEGF, have been linked to the disease’s pathology. Recent research has identified key signaling pathways including PI3K/Akt/mTOR and JAK-STAT3, as well as those regulated by type I IFN, as crucial in iMCD-TAFRO. These results suggest that dominant pathways may vary between subtypes. Further research into the peripheral blood and lymph nodes is required to determine the disease spectrum of iMCD-NOS/iMCD-TAFRO/TAFRO syndrome.
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(This article belongs to the Section Gene and Cell Therapy)
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Activation of CD14+ Monocytes via the IFN-γ Signaling Pathway Is Associated with Immune-Related Adverse Events in Hepatocellular Carcinoma Patients Receiving PD-1 Inhibition Combination Therapy
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Yaoru Song, Shida Pan, Jiahe Tian, Yingying Yu, Siyu Wang, Qin Qiu, Yingjuan Shen, Luo Yang, Xiaomeng Liu, Junqing Luan, Yilin Wang, Jianing Wang, Xing Fan, Fanping Meng and Fu-Sheng Wang
Biomedicines 2024, 12(6), 1140; https://doi.org/10.3390/biomedicines12061140 (registering DOI) - 21 May 2024
Abstract
(1) Background: Immune-related adverse events (irAEs) are a series of unique organ-specific inflammatory toxicities observed in patients with hepatocellular carcinoma (HCC) undergoing PD-1 inhibition combination therapy. The specific underlying mechanisms remain unclear. (2) Methods: We recruited 71 patients with HCC undergoing PD-1 inhibition
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(1) Background: Immune-related adverse events (irAEs) are a series of unique organ-specific inflammatory toxicities observed in patients with hepatocellular carcinoma (HCC) undergoing PD-1 inhibition combination therapy. The specific underlying mechanisms remain unclear. (2) Methods: We recruited 71 patients with HCC undergoing PD-1 inhibition combination therapy. These patients were then divided into two groups based on irAE occurrence: 34 had irAEs and 37 did not. Using Olink proteomics, we analyzed the aberrant inflammation-related proteins (IRPs) in these patient groups. For single-cell RNA sequencing (scRNA-seq) analysis, we collected peripheral blood mononuclear cells (PBMCs) from two representative patients at the pretreatment, irAE occurrence, and resolution stages. (3) Results: Our study revealed distinct plasma protein signatures in HCC patients experiencing irAEs after PD-1 inhibition combination therapy. We clarified the relationship between monocyte activation and irAEs, identified a strongly associated CD14-MC-CCL3 monocyte subset, and explored the role of the IFN-γ signaling pathway in monocyte activation during irAEs. (4) Conclusions: The activation of monocytes induced by the IFN-γ signaling pathway is an important mechanism underlying the occurrence of irAEs in HCC patients receiving PD-1 inhibition combination therapy.
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(This article belongs to the Section Immunology and Immunotherapy)
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Ovarian Stem Cells for Women’s Infertility: State of the Art
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Krzysztof Grettka, Katarzyna Idzik, Katarzyna Lewandowska, Ksena Świętek, Simone Palini and Franco Silvestris
Biomedicines 2024, 12(6), 1139; https://doi.org/10.3390/biomedicines12061139 (registering DOI) - 21 May 2024
Abstract
Today, women’s infertility is considered a social disease in females, occurring not only as an effect of POF (premature ovarian failure) but also as CTRI (cancer treatment-related infertility) in oncologic patients. Several procedures for FP (fertility preservation) are currently adopted to prevent this
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Today, women’s infertility is considered a social disease in females, occurring not only as an effect of POF (premature ovarian failure) but also as CTRI (cancer treatment-related infertility) in oncologic patients. Several procedures for FP (fertility preservation) are currently adopted to prevent this condition, mostly based on utilization of retrieved eggs from the patients with subsequent IVF (in vitro fertilization) or cryopreservation. However, great interest has recently been devoted to OSCs (ovarian stem cells), whose isolation from female ovaries, followed by their in vitro culture, led to their maturation to OLCs (oocyte-like cells), namely, neo-oocytes comparable to viable eggs suitable for IVF. Translation of these data to FP clinical application creates new hope in the treatment of infertility. Thus, in line with the significant progress in using stem cells in the regenerative medicine field, neo-oogenesis via OSCs, which is currently unapplicable in fertility preservation procedures, will provide novel possibilities for young and adult females in motherhood programs in the future.
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(This article belongs to the Special Issue Human Stem Cells in Disease Modelling and Treatment)
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The Role of Natural Products in Diabetic Retinopathy
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Yuxuan Zhao, Yi Chen and Naihong Yan
Biomedicines 2024, 12(6), 1138; https://doi.org/10.3390/biomedicines12061138 (registering DOI) - 21 May 2024
Abstract
Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus and potentially leads to significant visual impairment and blindness. The complex mechanisms involved in the pathological changes in DR make it challenging to achieve satisfactory outcomes with existing treatments. Diets
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Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus and potentially leads to significant visual impairment and blindness. The complex mechanisms involved in the pathological changes in DR make it challenging to achieve satisfactory outcomes with existing treatments. Diets conducive to glycemic control have been shown to improve outcomes in diabetic patients, thus positioning dietary interventions as promising avenues for DR treatment. Investigations have demonstrated that natural products (NPs) may effectively manage DR. Many types of natural compounds, including saponins, phenols, terpenoids, flavonoids, saccharides, alkaloids, and vitamins, have been shown to exert anti-inflammatory, antioxidant, anti-neovascular, and antiapoptotic effects in vivo and in vitro. Nevertheless, the clinical application of NPs still faces challenges, such as suboptimal specificity, poor bioavailability, and a risk of toxicity. Prospective clinical studies are imperative to validate the therapeutic potential of NPs in delaying or preventing DR.
Full article
(This article belongs to the Special Issue Molecular Research and Recent Advances in Diabetic Retinopathy)
Open AccessBrief Report
Effect of Hypoglycemia and Rebound Hyperglycemia on Proteomic Cardiovascular Risk Biomarkers
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Manjula Nandakumar, Thozhukat Sathyapalan, Stephen L. Atkin and Alexandra E. Butler
Biomedicines 2024, 12(6), 1137; https://doi.org/10.3390/biomedicines12061137 (registering DOI) - 21 May 2024
Abstract
Introduction: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii)
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Introduction: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii) severe iatrogenic hypoglycemia followed by rebound hyperglycemia. Methods: Two iatrogenic hypoglycemia studies were compared; firstly, mild hypoglycemia in 18 subjects (10 type 2 diabetes (T2D), 8 controls; blood glucose to 2.8 mmoL/L (50 mg/dL) for 1 h), and secondly, severe hypoglycemia in 46 subjects (23 T2D, 23 controls; blood glucose to <2.2 mmoL/L (<40 mg/dL) transiently followed by intravenous glucose reversal giving rebound hyperglycemia). A SOMAscan assay was used to measure 54 of the 92 cardiovascular protein biomarkers that reflect biomarkers involved in inflammation, cellular metabolic processes, cell adhesion, and immune response and complement activation. Results: Baseline to euglycemia showed no change in any of the proteins measured in the T2D cohort. With severe hypoglycemia, the study controls showed an increase in Angiopoietin 1 (ANGPT1) (p < 0.01) and Dickkopf-1 (DKK1) (p < 0.01), but no changes were seen with mild hypoglycemia. In both the mild and severe hypoglycemia studies, at the point of hypoglycemia, T2D subjects showed suppression of Brother of CDO (BOC) (p < 0.01). At 1 h post-hypoglycemia, the changes in ANGPT1, DKK1, and BOC had resolved, with no additional protein biomarker changes despite rebound hyperglycemia from 1.8 ± 0.1 to 12.2 ± 2.0 mmol/L. Conclusions: Proteomic biomarkers of cardiovascular disease showed changes at hypoglycemia that resolved within 1 h following the hypoglycemic event and with no changes following hyperglycemia rebound, suggesting that any cardiovascular risk increase is due to the hypoglycemia and not due to glucose fluctuation per se.
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(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
Open AccessArticle
Impact of Early Surfactant Administration on Ductus Arteriosus Assessed at 24 h in Preterm Neonates Less than 32 Weeks of Gestational Age
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Manuela Cucerea, Mihaela Moscalu, Maria-Livia Ognean, Amalia Fagarasan, Daniela Toma, Raluca Marian, Madalina Anciuc-Crauciuc, Andreea Racean, Zsuzsanna Gall and Marta Simon
Biomedicines 2024, 12(6), 1136; https://doi.org/10.3390/biomedicines12061136 - 21 May 2024
Abstract
Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤ 32 weeks of gestational age (GA) within 24 h of birth. Materials and Methods: It is a
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Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤ 32 weeks of gestational age (GA) within 24 h of birth. Materials and Methods: It is a prospective study conducted from 1 March 2022 to 31 December 2023 in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n = 44) and non-surfactant (n = 44) subgroups. Results: A total of 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler score at 24 h of life (1 − RR = 1 − 0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p = 0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p = 0.0178), pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p = 0.0210), and post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p = 0.0336). There were no significant changes in ductus arteriosus parameters at 24 h of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤ 32 weeks of gestational age at 24 h of life.
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(This article belongs to the Special Issue State-of-the-Art Surfactant in Biomedical Application: A Commemorative Issue in Honor of Prof. Tetsuro Fujiwara)
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Is There a Connection between Hyperhomocysteinemia and the Cardiometabolic Syndrome?
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Bogdan Mihai Tarcau, Andra Negru, Timea Claudia Ghitea and Eleonora Marian
Biomedicines 2024, 12(6), 1135; https://doi.org/10.3390/biomedicines12061135 - 21 May 2024
Abstract
This study investigates the distribution of hyperhomocysteinemia and cardiovascular metabolic syndrome (SM) among participants, shedding light on their prevalence and co-occurrence within the study cohort. Through an analysis of demographic characteristics and health parameters, including age, gender, and body mass index (BMI), alongside
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This study investigates the distribution of hyperhomocysteinemia and cardiovascular metabolic syndrome (SM) among participants, shedding light on their prevalence and co-occurrence within the study cohort. Through an analysis of demographic characteristics and health parameters, including age, gender, and body mass index (BMI), alongside nutritional data, correlations between these factors and health risks are explored. Results reveal a notable prevalence of hyperhomocysteinemia, with 45.3% of participants exhibiting this condition. Furthermore, 31.4% of the cohort does not present hyperhomocysteinemia or SM, while 23.3% shows SM without hyperhomocysteinemia. The study underscores gender-specific dietary recommendations due to significant variations in nutrient intake patterns. Additionally, inverse correlations between health risks like obesity, hypertension, and hypercholesterolemia and nutrient requirements highlight the need for tailored dietary interventions. Age-related changes in nutrient needs and the positive correlation between physical activity levels and certain nutrient demands further emphasize the importance of personalized dietary strategies. Variations in nutrient intake by gender, inverse correlations with health risks, and age-related changes underscore the need for tailored dietary strategies. These findings provide valuable insights for healthcare professionals in developing targeted nutritional interventions to mitigate disease risk and promote overall health and well-being.
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(This article belongs to the Special Issue Genetics, Obesity, Diabetes and Metabolic Syndrome)
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Iloperidone and Temozolomide Synergistically Inhibit Growth, Migration and Enhance Apoptosis in Glioblastoma Cells
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Sahar Mubeen, Iffat Raza, Badaruddin Ujjan, Bushra Wasim, Lubna Khan, Nadia Naeem, Syed Ather Enam and Farina Hanif
Biomedicines 2024, 12(6), 1134; https://doi.org/10.3390/biomedicines12061134 - 21 May 2024
Abstract
Glioblastoma (GBM) is a fatal astrocytic glioma with poor prognosis and treatment resistance. Repurposing potential FDA-approved drugs like anti-psychotics can address the concerns in a timely and cost-effective manner. Epidemiological studies have shown that patients with schizophrenic using anti-psychotics have a low incidence
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Glioblastoma (GBM) is a fatal astrocytic glioma with poor prognosis and treatment resistance. Repurposing potential FDA-approved drugs like anti-psychotics can address the concerns in a timely and cost-effective manner. Epidemiological studies have shown that patients with schizophrenic using anti-psychotics have a low incidence of GBM. Therefore, we aimed to investigate the therapeutic potential of atypical anti-psychotic Iloperidone (ILO) alone and in combination with Temozolomide (TMZ) against GBM. The study assessed the growth inhibitory effect of ILO, TMZ, and their combination (ILO + TMZ) on U-87MG and T-98G cell lines using an MTT assay. The drug interaction coefficient (CDI) was determined, and doses with synergistic effects were used for subsequent experiments, including migratory, invasion, and TUNEL assays. The expressions of DRD2, β-catenin, Dvl2, Twist, and Slug were assessed by RTq-PCR, whereas the β-catenin protein expression was also determined by immunocytochemistry. ILO (p < 0.05) and TMZ (p < 0.01) significantly inhibited the growth of U-87MG cells at all tested doses. The combination of 60 µM of both drugs showed synergistic activity with CDI < 1. The inhibition of migration and apoptosis was more pronounced in the case of combination treatment (p < 0.001). Inhibition of the invading cells was also found to be significant in ILO- and combination-treated groups (p < 0.001). ILO and combination treatment also significantly downregulated the expression of DRD2, while TMZ upregulated the expression (p < 0.001). The expressions of β-catenin (p < 0.001), Dvl2 (p < 0.001), Twist (p < 0.001), and Slug (p < 0.001) were also significantly downregulated in all treatment groups as compared to the vehicle control. The data suggest that ILO possesses strong growth inhibitory activity, possibly due to its effect on DRD2 and β-catenin expression and has the potential to be repurposed against GBM.
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(This article belongs to the Special Issue Glioblastoma: Current Status and Future Prospects)
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A Primer for Utilizing Deep Learning and Abdominal MRI Imaging Features to Monitor Autosomal Dominant Polycystic Kidney Disease Progression
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Chenglin Zhu, Xinzi He, Jon D. Blumenfeld, Zhongxiu Hu, Hreedi Dev, Usama Sattar, Vahid Bazojoo, Arman Sharbatdaran, Mohit Aspal, Dominick Romano, Kurt Teichman, Hui Yi Ng He, Yin Wang, Andrea Soto Figueroa, Erin Weiss, Anna G. Prince, James M. Chevalier, Daniil Shimonov, Mina C. Moghadam, Mert Sabuncu and Martin R. Princeadd
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Biomedicines 2024, 12(5), 1133; https://doi.org/10.3390/biomedicines12051133 - 20 May 2024
Abstract
Abdominal imaging of autosomal dominant polycystic kidney disease (ADPKD) has historically focused on detecting complications such as cyst rupture, cyst infection, obstructing renal calculi, and pyelonephritis; discriminating complex cysts from renal cell carcinoma; and identifying sources of abdominal pain. Many imaging features of
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Abdominal imaging of autosomal dominant polycystic kidney disease (ADPKD) has historically focused on detecting complications such as cyst rupture, cyst infection, obstructing renal calculi, and pyelonephritis; discriminating complex cysts from renal cell carcinoma; and identifying sources of abdominal pain. Many imaging features of ADPKD are incompletely evaluated or not deemed to be clinically significant, and because of this, treatment options are limited. However, total kidney volume (TKV) measurement has become important for assessing the risk of disease progression (i.e., Mayo Imaging Classification) and predicting tolvaptan treatment’s efficacy. Deep learning for segmenting the kidneys has improved these measurements’ speed, accuracy, and reproducibility. Deep learning models can also segment other organs and tissues, extracting additional biomarkers to characterize the extent to which extrarenal manifestations complicate ADPKD. In this concept paper, we demonstrate how deep learning may be applied to measure the TKV and how it can be extended to measure additional features of this disease.
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(This article belongs to the Special Issue Pathogenesis and Treatment Progress of Chronic Kidney Diseases Volume II)
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Comparative Evaluation of Dental Enamel Microhardness Following Various Methods of Interproximal Reduction: A Vickers Hardness Tester Investigation
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Dan-Cosmin Serbanoiu, Aurel-Claudiu Vartolomei, Dana-Valentina Ghiga, Silvia Izabella Pop, Irinel Panainte, Marioara Moldovan, Codruta Sarosi, Ioan Petean, Marie-Jose Boileau and Mariana Pacurar
Biomedicines 2024, 12(5), 1132; https://doi.org/10.3390/biomedicines12051132 - 20 May 2024
Abstract
Interproximal enamel reduction, also known as stripping, is a common orthodontic procedure that reduces the mesiodistal diameter of teeth, allowing for a balance of available space in dental arches. The aim of this study was to assess the enamel surface microhardness resulting from
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Interproximal enamel reduction, also known as stripping, is a common orthodontic procedure that reduces the mesiodistal diameter of teeth, allowing for a balance of available space in dental arches. The aim of this study was to assess the enamel surface microhardness resulting from the application of currently available methods for interproximal reduction. Forty-two extracted human permanent teeth were divided into six different groups, each subjected to a therapeutic stripping procedure using various methods (i.e., diamond burs, abrasive strips of 90 μm, 60 μm, 40 μm, and 15 μm, and abrasive discs). Stripping was performed by a single individual in accordance with the manufacturers’ recommendations for the various systems used. One of the proximal faces of the tooth underwent IPR, while the other side remained untreated for control. The hardness of the enamel surface was measured using a Vickers hardness tester. The control group achieved the hardest enamel surface (354.4 ± 41.02 HV1), while the lowest was observed for enamel surfaces treated with 90 µm abrasive strips (213.7 ± 118.6). The only statistically significant difference was identified in comparisons between the values measured for the control group and those obtained after stripping with diamond burs (p = 0.0159). Enamel microhardness varied depending on the stripping instrument used, but no statistically significant differences were found (p > 0.05). Optimal microhardness values, close to those of healthy enamel, were achieved after mechanical treatment with 15 µm abrasive strips and abrasive discs. Dental stripping is a safe therapeutic procedure that has a relatively minor influence on the microhardness of surface enamel.
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(This article belongs to the Section Molecular and Translational Medicine)
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Can Microfluidics Improve Sperm Quality? A Prospective Functional Study
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Fernando Meseguer, Carla Giménez Rodríguez, Rocío Rivera Egea, Laura Carrión Sisternas, Jose A. Remohí and Marcos Meseguer
Biomedicines 2024, 12(5), 1131; https://doi.org/10.3390/biomedicines12051131 - 20 May 2024
Abstract
The same sperm selection techniques in assisted reproduction clinics have remained largely unchanged despite their weaknesses. Recently, microfluidic devices have emerged as a novel methodology that facilitates the sperm selection process with promising results. A prospective case-control study was conducted in two phases:
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The same sperm selection techniques in assisted reproduction clinics have remained largely unchanged despite their weaknesses. Recently, microfluidic devices have emerged as a novel methodology that facilitates the sperm selection process with promising results. A prospective case-control study was conducted in two phases: 100 samples were used to compare the microfluidic device with Density Gradient, and another 100 samples were used to compare the device with the Swim-up. In the initial phase, a significant enhancement in progressive motility, total progressive motile sperm count, vitality, morphology, and sperm DNA fragmentation were obtained for the microfluidic group compared to Density Gradient. Nevertheless, no statistically significant differences were observed in sperm concentration and chromatin structure stability. In the subsequent phase, the microfluidic group exhibited significant increases in sperm concentration, total progressive motile sperm count, and vitality compared to Swim-up. However, non-significant differences were seen for progressive motility, morphology, DNA structure stability, and DNA fragmentation. Similar trends were observed when results were stratified into quartiles. In conclusion, in a comparison of microfluidics with standard techniques, an improvement in sperm quality parameters was observed for the microfluidic group. However, this improvement was not significant for all parameters.
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(This article belongs to the Special Issue Molecular Regulation of Spermatozoa)
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Exploring the Role of Guanylate-Binding Protein-2 in Activated Microglia-Mediated Neuroinflammation and Neuronal Damage
by
Ji-Eun You, Eun-Ji Kim, Ho Won Kim, Jong-Seok Kim, Kyunggon Kim and Pyung-Hwan Kim
Biomedicines 2024, 12(5), 1130; https://doi.org/10.3390/biomedicines12051130 - 20 May 2024
Abstract
Neuron damage by microglia, which act as macrophage cells in the brain, can result in various brain diseases. However, the function of pro-inflammatory or anti-inflammatory microglia in the neurons remains controversial. Guanylate-binding protein-2 (GBP2) is expressed and activated in the microglia in the
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Neuron damage by microglia, which act as macrophage cells in the brain, can result in various brain diseases. However, the function of pro-inflammatory or anti-inflammatory microglia in the neurons remains controversial. Guanylate-binding protein-2 (GBP2) is expressed and activated in the microglia in the early phase of the inflammatory response and plays an important role in controlling immune responses. In this study, we evaluated whether GBP2 initially reduces the immune response induced by microglia, and whether microglia induce pro-inflammatory functions in neurons via GBP2 expression. In lipopolysaccharide (LPS)-stimulated microglia, we assessed the expression of GBP2 and how it affects neurons via activated microglia. The biological functions of microglia due to the downregulation of the GBP2 gene were examined using short hairpin RNA (shRNA)-RNA-GBP2. Downregulated GBP2 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Furthermore, this protein was observed to be highly expressed in the brains of dementia mice. Our results are the first to report that the downregulation of GBP2 in activated microglia has an anti-inflammatory function. This study suggests that the GBP2 gene can be used as a therapeutic target biomarker for inflammation-related neurodegenerative diseases.
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(This article belongs to the Section Immunology and Immunotherapy)
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Regulation of the Function and Expression of EpCAM
by
Di Xiao, Mingrui Xiong, Xin Wang, Mengqing Lyu, Hanxiang Sun, Yeting Cui, Chen Chen, Ziyu Jiang and Fan Sun
Biomedicines 2024, 12(5), 1129; https://doi.org/10.3390/biomedicines12051129 - 20 May 2024
Abstract
The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target
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The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target for cancer therapy. As a cell adhesion molecule, EpCAM has a crystal structure that indicates that it forms a cis-dimer first and then probably a trans-tetramer to mediate intercellular adhesion. Through regulated intramembrane proteolysis (RIP), EpCAM and its proteolytic fragments are also able to regulate multiple signaling pathways, Wnt signaling in particular. Although great progress has been made, increasingly more findings have revealed the context-specific expression and function patterns of EpCAM and their regulation processes, which necessitates further studies to determine the structure, function, and expression of EpCAM under both physiological and pathological conditions, broadening its application in basic and translational cancer research.
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(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
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Characterizing the Dynamic Expression of C1q/TNF-α-Related Protein 6 (CTRP6) during Pregnancy in Humans and Mice with Gestational Diabetes Mellitus
by
Jianan Jiang, Shuangyu Wei, Miao Chen, Yutian Tan, Zhao Yang, Guiying Yang, Weijie Feng, Zhen Han, Xiaojing Wei and Xiao Luo
Biomedicines 2024, 12(5), 1128; https://doi.org/10.3390/biomedicines12051128 - 19 May 2024
Abstract
Aim: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. Methods: Chinese Han pregnant women (GDM n =
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Aim: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. Methods: Chinese Han pregnant women (GDM n = 9, control n = 10) with a scheduled caesarean section delivery were recruited. A number of high-fat diet (HFD) induced-pregnancy C57BL/6 mice were chosen as an animal model of GDM. Circulating levels of CTRP6 and adiponectin were examined by ELISA. CTRP6 expression in adipose tissue and placenta were detected by real-time qPCR and WB. Result: Plasma CTRP6 levels were decreased during the first and second trimesters in mice, as well as the second and third trimesters in patients, while they were increased at delivery in GDM patients and mice. Plasma CTRP6 levels were significantly correlated with WBC, systolic pressure, diastolic pressure and fasting blood glucose. Moreover, CTRP6 mRNA expression in the subcutaneous (sWAT) and omental white adipose tissue (oWAT), as well as in the placenta, was significantly higher in GDM human patients at cesarean delivery. Furthermore, the mRNA expression of Ctrp6 was increased in the sWAT and visceral WAT (vWAT), whilst decreased in the interscapular brown adipose tissue (iBAT), of GDM mice at cesarean delivery. Conclusion: Dynamically expressed CTRP6 may be served as a candidate target for treatment of GDM.
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(This article belongs to the Section Endocrinology and Metabolism Research)
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Associations of Diabetes and Hyperglycaemia with Extent and Outcomes of Acute Burn Injuries
by
Jeffrey Chandra, Edward Raby, Fiona M. Wood, P. Gerry Fegan and Bu B. Yeap
Biomedicines 2024, 12(5), 1127; https://doi.org/10.3390/biomedicines12051127 - 19 May 2024
Abstract
Background: Severe burns may induce hyperglycaemia in the absence of diabetes, but how glucose trajectories relate to burns outcomes is unclear. Aim: To assess incidence of hyperglycaemia following acute burn injury, and associations with diabetes history and length of stay (LOS). Methods: Retrospective
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Background: Severe burns may induce hyperglycaemia in the absence of diabetes, but how glucose trajectories relate to burns outcomes is unclear. Aim: To assess incidence of hyperglycaemia following acute burn injury, and associations with diabetes history and length of stay (LOS). Methods: Retrospective cohort study of adults admitted with acute burns to tertiary centres. Blood glucose level (BGL), hyperglycaemic episodes (BGL ≥ 11.1 mmol/L) and hyperglycaemic days were recorded. Stress hyperglycaemia was defined as BGL ≥ 11.1 mmol/L without a diabetes history. Results: A total of 30 participants had a diabetes history and 260 did not. Participants with known diabetes had higher mean BGLs (9.7 vs. 9.0 mmol/L, p < 0.001), more hyperglycaemic episodes (28.0 vs. 17.2%, p < 0.001) and hyperglycaemic days (51 vs. 21%, p < 0.001), compared to those without diabetes, despite smaller burns (total body surface area 1.0 vs. 14.8%, p < 0.001). Fourteen participants with stress hyperglycaemia had similar BGLs (at admission 10.3 vs. 11.5 mmol/L; during inpatient stay 9.9 vs. 9.8 mmol/L), more severe burns (15.6% vs. 1.0% TBSA) and longer LOS (18 vs. 7 days, p < 0.001) compared to participants with known diabetes. Extent of burns, having NGT nutrition, age, having inpatient BGL monitoring in the setting of diabetes, or having inpatient BGL monitoring in the absence of diabetes were associated with longer LOS. Conclusions: In participants with known diabetes, small burn injuries were associated with hyperglycaemia. Stress hyperglycaemia can be triggered by major burn injuries, with early and sustained elevation of BGLs. Further research is warranted to improve inpatient management of BGL in patients with acute burn injury.
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(This article belongs to the Section Endocrinology and Metabolism Research)
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Insights into Kidney Dysplasia in Duplex Kidneys: From Radiologic Diagnosis to Histopathologic Understanding
by
Dominik Świętoń, Kamil Buczkowski, Piotr Czarniak, Andrzej Gołębiewski, Małgorzata Grzywińska, Mariusz J. Kujawa, Susan J. Back, Maciej Piskunowicz and Ewa Iżycka-Świeszewska
Biomedicines 2024, 12(5), 1126; https://doi.org/10.3390/biomedicines12051126 - 18 May 2024
Abstract
Duplex kidney is a urinary tract anomaly commonly associated with a wide range of primary and secondary parenchymal structural abnormalities. We present a unique comparison of US and MRI findings with histopathology following partial resection of duplex kidneys due to nephropathy. We examined
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Duplex kidney is a urinary tract anomaly commonly associated with a wide range of primary and secondary parenchymal structural abnormalities. We present a unique comparison of US and MRI findings with histopathology following partial resection of duplex kidneys due to nephropathy. We examined a group of 21 children with duplex kidneys who were qualified for heminephrectomy (24 kidney units (KU)). All patients underwent US and MRI prior to the surgery. The imaging results were compared with histopathologic findings. In 21/24 KU, dysplastic changes were found on histopathology, including all with obstructive nephropathy and 7/10 specimens with refluxing uropathy. The loss of corticomedullary differentiation on US and increased signal on T2-weighted images (T2WI) on MRI were the imaging findings that best correlated with fibrosis. In children with megaureter, there were no statistical differences in histopathological findings between primary megaureter, megaureter with ureterocele, and megaureter with ectopia (p > 0.05). The extent of dysplasia of the affected pole correlated negatively with residual function in MRI. Kidney dysplasia and inflammation in the kidney with obstructive nephropathy are the most important histopathologic findings of this study. US is a valuable screening tool, and MRI enables morphologic and functional assessments of the nephropathy in duplex kidneys.
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(This article belongs to the Section Cell Biology and Pathology)
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