Biomedicines

15 pages, 2590 KiB

Open AccessArticle

Evaluating the Effectiveness of Ultrasound-Guided Subacromial-Subdeltoid Bursa and Coracohumeral Ligament Corticosteroid Injections With and Without Physiotherapy in Adhesive Capsulitis Treatment

by Chu-Wen Tang, Ting-Yu Lin, Peng-Chieh Shen and Fuk-Tan Tang

Biomedicines 2024, 12(12), 2668; https://doi.org/10.3390/biomedicines12122668 - 22 Nov 2024

Abstract

Background: The objective of this study was to investigate the effect of ultrasound-guided corticosteroid injection to the subacromial-subdeltoid bursa (SSB) and coracohumeral ligament (CHL) in treating adhesive capsulitis, with a particular focus on evaluating the potential benefits of regular electrotherapy and conventional [...] Read more.

Background: The objective of this study was to investigate the effect of ultrasound-guided corticosteroid injection to the subacromial-subdeltoid bursa (SSB) and coracohumeral ligament (CHL) in treating adhesive capsulitis, with a particular focus on evaluating the potential benefits of regular electrotherapy and conventional rehabilitation exercises. Methods: A total of 29 patients with unilateral shoulder pain and restricted shoulder range of motion (ROM) were included. Corticosteroids were delivered to the subacromial-subdeltoid bursa (SSB) and coracohumeral ligament (CHL) through a single percutaneous injection. Group 1 consisted of 18 patients who received injections only, while Group 2 comprised 11 patients who received injections in combination with regular physiotherapy. Shoulder Pain and Disability Index (SPADI) scores and ROM were assessed before the injection, and again at 4, 8, and 12 weeks following the intervention. A multivariate mixed-effects model with repeated measurements was conducted for the variables. Results: Electrotherapy and traditional rehabilitation exercises did not enhance the effectiveness of this injection approach. Pain, upper extremity function, and ROM in all planes were all significantly improved with a corticosteroid injection to the CHL and SSB. Conclusions: Physiotherapy did not offer additional benefits when combined with ultrasound-guided corticosteroid injection to the CHL and SSB. The injection alone significantly improved pain, disability, and ROM in patients with adhesive capsulitis. Further research is required to optimize current physiotherapy with electrotherapy and traditional rehabilitation exercises after ultrasound-guided corticosteroid injections. Full article

(This article belongs to the Special Issue Tendinopathy and Myopathy: From Molecular Basis to Therapy)

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23 pages, 5624 KiB

Open AccessArticle

RELT Is Upregulated in Breast Cancer and Induces Death in Breast Cancer Cells

by Maryann Batiste, Bethany Joy, Cara K. Yee, Luke Cho, Ashley Christensen, Ihab Abed, Kailey Nguyen, Anusri Yanumula, Hannah Chang, Evan D. Cho, Wenjia Wang, Emily Chou, Esther H. Chang, Yennie L. Shyu, Alyssa Abram, Jessa Alcaide, James Zhou, Brittany Gillespie, Michelle Senderovich, Gianne Almeida Cusick, Ai-Vy Le, Frank Hoang, Yihui Shi, Eslam Mohamed and John K. Cusick Show full author list Hide full author list

Biomedicines 2024, 12(12), 2667; https://doi.org/10.3390/biomedicines12122667 - 22 Nov 2024

Abstract

Background: Receptor Expressed in Lymphoid Tissues (RELT) is a TNFRSF member that has two paralogs, RELL1 and RELL2; the three proteins are collectively referred to as RELT family members (RELTfms). Methods: We sought to evaluate RELT expression in cancerous cells by using real-time [...] Read more.

Background: Receptor Expressed in Lymphoid Tissues (RELT) is a TNFRSF member that has two paralogs, RELL1 and RELL2; the three proteins are collectively referred to as RELT family members (RELTfms). Methods: We sought to evaluate RELT expression in cancerous cells by using real-time PCR, western blotting, flow cytometry, and immunohistochemistry (IHC). The mechanism of RELT-induced cell death was assessed by western blotting, flow cytometry, luciferase assays, and morphology staining. RELT localization was detected through immunofluorescence and western blotting, and co-immunoprecipitation was used to test whether a mutated RELT interacts with the OXSR1 kinase. Results: RELT and RELL1 protein expression was significantly elevated in cell lines representing breast and lung cancer, whereas RELL2 protein expression was relatively consistent across different cell lines. The surface expression of RELT was highest in monocytes. IHC staining revealed increased RELT expression in malignant breast cancer biopsies compared to patient-matched benign tissue. RELTfm overexpression induced death in MDA-MB-231 (231) breast cancer cells, accompanied by increased phosphatidylserine externalization and Caspase-3/7 activation. The co-transfection of plasmids predicted to block the phosphorylation of RELT by the OXSR1 kinase did not abrogate RELT-induced apoptosis, indicating that the activation of p38 by RELT through the OXSR1 kinase is not required for RELT-induced cell death. Interestingly, nuclear localization of RELT was detected in 231 and HEK-293 cells. Conclusions: These results demonstrate that RELT induces death in breast cancer cells through an apoptotic pathway that does not require OXSR1 phosphorylation and that RELT possesses the ability to translocate to the nucleus, a novel finding that warrants further investigation. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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14 pages, 4335 KiB

Open AccessArticle

Murine vs. Human Osteoblast Responses to Coagulation and Inflammatory Factors: Reconsidering the Use of Animal Models in Hemophilia a Research

by Aline Bernar, Monika Bauer, Michael Schirmer, Werner Streif and Jennifer Gebetsberger

Biomedicines 2024, 12(12), 2666; https://doi.org/10.3390/biomedicines12122666 - 22 Nov 2024

Abstract

Background/Objectives: Hemophilia A is associated with frequent bleeding episodes, joint damage, and reduced bone mineral density (BMD). The role of coagulation factors and inflammatory cytokines on bone metabolism, particularly on osteoblast function, is of increasing interest. However, significant inter-species differences in bone [...] Read more.

Background/Objectives: Hemophilia A is associated with frequent bleeding episodes, joint damage, and reduced bone mineral density (BMD). The role of coagulation factors and inflammatory cytokines on bone metabolism, particularly on osteoblast function, is of increasing interest. However, significant inter-species differences in bone remodeling raise concerns about the translatability of findings from murine models to human systems. This study aims to investigate the effects of human coagulation factors and cytokines on bone formation, focusing on inter-species differences in the cell viability and mineralization of murine and human osteoblasts. Methods: Murine MC3T3-E1 and human SaOs-2 osteoblasts were cultured in osteoblast differentiation medium supplemented with various coagulation factors (FVIII, vWF, vWF-FVIII, FIX, FX, thrombin, and FVIII-thrombin) or cytokines (IL-6, TNF-α). Cell viability was assessed at both two-week and three-week time points using the CCK-8 assay, and mineralization was evaluated via Alizarin red S staining. Results: Coagulation factors significantly enhanced cell viability in human osteoblasts but had no effects on the murine counterpart. FX inhibited mineralization in human cells, while murine cells showed no significant changes. TNF-α stimulated mineralization in murine osteoblasts but inhibited it in human cells, highlighting species-specific responses to inflammatory cytokines. Similar trends in response patterns were observed at two and three weeks, with greater consistency at the later time point. Conclusions: These findings reveal critical inter-species differences in osteoblast responses to coagulation factors and cytokines, raising questions about the validity of using murine models to study human bone metabolism. Future research must account for these differences to ensure that preclinical models accurately reflect human pathophysiology, particularly in the context of hemophilia A. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases 2.0)

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18 pages, 2429 KiB

Open AccessReview

The Role of Extracellular Vesicles in Liver Fibrosis: Friends or Foes?

by Xiang Tao, Can Chen and Mei Liu

Biomedicines 2024, 12(12), 2665; https://doi.org/10.3390/biomedicines12122665 - 22 Nov 2024

Abstract

Liver fibrosis represents a common pathway in the progression of various chronic liver diseases towards cirrhosis and liver failure. Extracellular vesicles (EVs) are membrane-enclosed particles secreted by diverse cell types, including exosomes, microvesicles, apoptotic vesicles, and the recently identified migrasomes. These vesicles can [...] Read more.

Liver fibrosis represents a common pathway in the progression of various chronic liver diseases towards cirrhosis and liver failure. Extracellular vesicles (EVs) are membrane-enclosed particles secreted by diverse cell types, including exosomes, microvesicles, apoptotic vesicles, and the recently identified migrasomes. These vesicles can be taken up by recipient cells, thereby modulating their function through the transport of cargo molecules. EVs facilitate intercellular communication and play a significant role in the development of liver fibrosis. Moreover, the detection of EVs in various body fluids offers sensitive diagnostic tools for assessing liver fibrosis. Additionally, EVs may serve as therapeutic targets, potential therapeutic agents, and drug delivery vehicles. This article reviews recent advances in the field of EVs concerning liver fibrosis and related diseases, with a particular focus on the potential role of the newly discovered migrasomes in intracellular crosstalk within the liver. Full article

(This article belongs to the Section Cell Biology and Pathology)

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17 pages, 1139 KiB

Open AccessReview

Predictive and Prognostic Significance of Molecular Biomarkers in Glioblastoma

by Siddharth Shah, Aiswarya Nag, Sirpi Vivekanandam Sachithanandam and Brandon Lucke-Wold

Biomedicines 2024, 12(12), 2664; https://doi.org/10.3390/biomedicines12122664 - 22 Nov 2024

Abstract

Glioblastoma multiforme (GBM), a WHO grade 4 glioma, is the most common and aggressive primary brain tumor, characterized by rapid progression and poor prognosis. The heterogeneity of GBM complicates diagnosis and treatment, driving research into molecular biomarkers that can offer insights into tumor [...] Read more.

Glioblastoma multiforme (GBM), a WHO grade 4 glioma, is the most common and aggressive primary brain tumor, characterized by rapid progression and poor prognosis. The heterogeneity of GBM complicates diagnosis and treatment, driving research into molecular biomarkers that can offer insights into tumor behavior and guide personalized therapies. This review explores recent advances in molecular biomarkers, highlighting their potential to improve diagnosis and treatment outcomes in GBM patients. Key biomarkers such as MGMT promoter methylation, IDH1/2 mutations, EGFR amplification, and TERT promoter mutations, etc., are examined for their roles in prognosis, therapeutic response, and tumor classification. While molecular biomarkers offer valuable insights for tailoring GBM treatments, their clinical application is hindered by tumor heterogeneity, dynamic genetic evolution, and the lack of standardized testing methods. Future research should aim to confirm new biomarkers and incorporate them into regular clinical practice to improve prognosis and treatment choices. Advances in genomic and proteomic technologies, along with consistent biomarker detection, could transform GBM care and enhance patient outcomes. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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18 pages, 2217 KiB

Open AccessArticle

Clinical and Genetic Characterization of Adolescent-Onset Epilepsy: A Single-Center Experience in Republic of Korea

by Ji Yoon Han, Tae Yun Kim and Joonhong Park

Biomedicines 2024, 12(12), 2663; https://doi.org/10.3390/biomedicines12122663 - 22 Nov 2024

Abstract

Objectives: This study investigated the characteristics of adolescent-onset epilepsy (AOE) and conducted genetic tests on a cohort of 76 Korean patients to identify variants and expand the spectrum of mutations associated with AOE. Methods: Clinical exome sequencing after routine karyotyping and chromosomal microarray [...] Read more.

Objectives: This study investigated the characteristics of adolescent-onset epilepsy (AOE) and conducted genetic tests on a cohort of 76 Korean patients to identify variants and expand the spectrum of mutations associated with AOE. Methods: Clinical exome sequencing after routine karyotyping and chromosomal microarray was performed to identify causative variants and expand the spectrum of mutations associated with AOE. Results: In cases of AOE without neurodevelopmental delay (NDD), this study identified four likely pathogenic variants (LPVs) or variants of uncertain significance (VUS) and two copy number variations (CNVs). To explore the unique features of AOE; clinical manifestations were compared between patients with and without NDD. The analysis revealed statistically significant differences in the prevalence of males and the yield of genetic testing results. AOE without NDD had a lower prevalence in males (49%) compared to AOE with NDD (60%) (p = 0.007). Genetic alterations: AOE with NDD exhibited a higher frequency of genetic alterations (35%) compared to AOE without NDD (12%) (p = 0.011). Thorough evaluation of AOE can be particularly challenging in adolescent patients. Some individuals may display genetic variations due to a phenomenon known as locus heterogeneity, where different genetic causes lead to similar clinical presentations. Conclusions: Implementing a robust genetic workflow is crucial for accurately diagnosing AOE, even in cases with complex genetic underpinnings. This study underscores the importance of genetic testing as an essential diagnostic tool for AOE. Identifying genetic variants and understanding their clinical correlations can aid in improving diagnostic accuracy and optimizing treatment approaches for adolescent patients with epilepsy. Full article

(This article belongs to the Special Issue Neurodevelopmental Disorders: From Pathophysiology to Novel Therapeutic Approaches—2nd Edition)

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27 pages, 3640 KiB

Open AccessReview

The Crosstalk Between Cartilage and Bone in Skeletal Growth

by Frank Hernández-García, Ángela Fernández-Iglesias, Julián Rodríguez Suárez, Helena Gil Peña, José M. López and Rocío Fuente Pérez

Biomedicines 2024, 12(12), 2662; https://doi.org/10.3390/biomedicines12122662 - 21 Nov 2024

Abstract

While the flat bones of the face, most of the cranial bones, and the clavicles are formed directly from sheets of undifferentiated mesenchymal cells, most bones in the human body are first formed as cartilage templates. Cartilage is subsequently replaced by bone via [...] Read more.

While the flat bones of the face, most of the cranial bones, and the clavicles are formed directly from sheets of undifferentiated mesenchymal cells, most bones in the human body are first formed as cartilage templates. Cartilage is subsequently replaced by bone via a very tightly regulated process termed endochondral ossification, which is led by chondrocytes of the growth plate (GP). This process requires continuous communication between chondrocytes and invading cell populations, including osteoblasts, osteoclasts, and vascular cells. A deeper understanding of these signaling pathways is crucial not only for normal skeletal growth and maturation but also for their potential relevance to pathophysiological processes in bones and joints. Due to limited information on the communication between chondrocytes and other cell types in developing bones, this review examines the current knowledge of how interactions between chondrocytes and bone-forming cells modulate bone growth. Full article

(This article belongs to the Special Issue Advances in Chondrocyte Biology)

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15 pages, 1823 KiB

Open AccessArticle

by Milica Dekleva, Tamara Djuric, Ana Djordjevic, Ivan Soldatovic, Aleksandra Stankovic, Jelena Suzic Lazic and Maja Zivkovic

Biomedicines 2024, 12(12), 2661; https://doi.org/10.3390/biomedicines12122661 - 21 Nov 2024

Abstract

Backgrounds: Galectin-3 (gal-3) is upregulated in remodeling, and failing myocardium and gal-3 levels are increased in hypertrophy, fibrosis and inflammation. The aim of this study was to investigate the potential role of sex-related differences in the following: risk factors, left ventricular (LV) structural [...] Read more.

Backgrounds: Galectin-3 (gal-3) is upregulated in remodeling, and failing myocardium and gal-3 levels are increased in hypertrophy, fibrosis and inflammation. The aim of this study was to investigate the potential role of sex-related differences in the following: risk factors, left ventricular (LV) structural and functional changes, coronary angiography, expression of the gal-3 encoding gene LGALS-3 and plasma gal-3 levels in heart failure (HF). Materials and Methods: This prospective study included 137 men and 44 women with first MI who underwent Doppler echocardiography within 2–4 days of MI and after 6 months. Relative LGALS-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) was detected using TaqMan^® technology. Plasma gal-3 concentration was determined by ELISA method. Results: In the acute phase of MI, LV end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were significantly lower in women compared to men (58.2 ± 13.1 vs. 46.3 ± 11.1, p < 0.001; 33.7 ± 9.5 vs. 27.0 ± 9.2, p < 0.001, respectively). The incidence of LV hypertrophy (LVH) and HF was significantly higher in women compared to men (70.0% vs. 44.6%, p = 0.03; 37.5% vs.19.5%, p = 0.02, respectively). There was a significant correlation between the grade of LV diastolic dysfunction (LVDD) and plasma gal-3 levels (p < 0.001). The relative expression of LGALS-3 mRNA in PBMCs was higher in females (fold induction = 1.326, S.E. range = 0.748–2.587, p = 0.007). Plasma gal-3 levels were higher in women compared to men (44.66 ± 28.04 vs. 16.30 ± 12.68, p < 0.001) and higher in patients with HF than in patients without HF (31.14 ± 27.09 vs.21.39 ± 18.17, p = 0.025). Conclusions: Gender-specific factors such as LVH, LVDD, LGALS-3 mRNA expression and plasma gal-3 levels may explain the increased incidence of HF in women. The differences in the model and determinants of HF between men and women may be relevant for further therapeutic strategies including the inhibition of gal-3. Full article

(This article belongs to the Special Issue Molecular Insights into Myocardial Infarction)

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10 pages, 4362 KiB

Open AccessArticle

The HuRaA Trial—The Radiocapitellar Line Shows Significant Posterior Translation in Healthy Elbows: A Prospective Analysis of 53 Healthy Individuals

by Christian T. Schamberger, Tobias Grossner, Christoph Rehnitz, Sebastian Findeisen, Thomas Ferbert, Arnold J. Suda, Gerhard Schmidmaier and Stephan Stein

Biomedicines 2024, 12(12), 2660; https://doi.org/10.3390/biomedicines12122660 - 21 Nov 2024

Abstract

Background: The elbow joint is stabilized by complex interactions between bony structures and soft tissues, notably the lateral and medial collateral ligaments. Posterolateral rotatory instability (PLRI), a form of elbow instability, is challenging to diagnose due to overlapping symptoms with other conditions. [...] Read more.

Background: The elbow joint is stabilized by complex interactions between bony structures and soft tissues, notably the lateral and medial collateral ligaments. Posterolateral rotatory instability (PLRI), a form of elbow instability, is challenging to diagnose due to overlapping symptoms with other conditions. The radiocapitellar line (RCL) is a radiographic tool for assessing humeroradial alignment and elbow stability, but its diagnostic accuracy remains debated. This study aims to provide normative data on RCL deviations in healthy individuals to improve diagnostic criteria for PLRI. Methods: A prospective study was conducted with 53 healthy individuals (27 males, 26 females) aged 18–45 years. MRI scans of the participants’ elbows were performed in maximum extension and supination to assess radiocapitellar deviations (RCDs). Two orthopedic surgeons independently analyzed the images to evaluate RCDs and assess interobserver reliability. Statistical analyses, including independent t-tests and Pearson correlations, were used to explore the relationship between RCDs, demographic factors, and elbow stability. Results: The average RCD in the cohort was 1.77 mm (SD 1.06 mm). Notably, 62.9% of participants had deviations greater than 1.2 mm, while 12.9% exceeded 3.4 mm, thresholds traditionally used to diagnose PLRI. Gender and age did not significantly influence RCD values. The interobserver reliability was almost good (ICC = 0.87), supporting the consistency of the RCL measurements. Conclusions: Significant RCDs occur even in asymptomatic individuals, challenging the current diagnostic thresholds for PLRI based solely on RCL measurements. A comprehensive assessment that includes clinical, anatomical, and functional evaluations is essential for accurate diagnosis. These findings highlight the need for refined diagnostic criteria and further research into elbow stability. Full article

(This article belongs to the Special Issue Musculoskeletal Injuries: Clinical, Radiological, and Biochemical Evaluation in Orthopedics)

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29 pages, 1439 KiB

Open AccessReview

Diagnostics and Therapy for Malignant Tumors

by Chung-Che Tsai, Chun-Yu Wang, Hsu-Hung Chang, Phebe Ting Syuan Chang, Chuan-Hsin Chang, Tin Yi Chu, Po-Chih Hsu and Chan-Yen Kuo

Biomedicines 2024, 12(12), 2659; https://doi.org/10.3390/biomedicines12122659 - 21 Nov 2024

Abstract

Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature of these tumors requires multifaceted diagnostic and therapeutic approaches. This review explores current advancements in diagnostic methods, including molecular [...] Read more.

Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature of these tumors requires multifaceted diagnostic and therapeutic approaches. This review explores current advancements in diagnostic methods, including molecular imaging, biomarkers, and liquid biopsies. It also delves into the evolution of therapeutic strategies, including surgery, chemotherapy, radiation therapy, and novel targeted therapies such as immunotherapy and gene therapy. Although significant progress has been made in the understanding of cancer biology, the future of oncology lies in the integration of precision medicine, improved diagnostic tools, and personalized therapeutic approaches that address tumor heterogeneity. This review aims to provide a comprehensive overview of the current state of cancer diagnostics and treatments while highlighting emerging trends and challenges that lie ahead. Full article

(This article belongs to the Special Issue Diagnostics and Therapy for Malignant Tumors: New Developments)

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17 pages, 1212 KiB

Open AccessReview

The Role of microRNA-155 as a Biomarker in Diffuse Large B-Cell Lymphoma

by Epameinondas Koumpis, Vasileios Georgoulis, Konstantina Papathanasiou, Alexandra Papoudou-Bai, Panagiotis Kanavaros, Evangelos Kolettas and Eleftheria Hatzimichael

Biomedicines 2024, 12(12), 2658; https://doi.org/10.3390/biomedicines12122658 - 21 Nov 2024

Abstract

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with [...] Read more.

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL pathogenesis, since miR-155 regulates key pathways, transcription factors and cytokine expression and shapes the tumor microenvironment in DLBCL. In this review, we examine the role of miR-155 in DLBCL and its potential as a future diagnostic, prognostic, or predictive biomarker. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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14 pages, 28180 KiB

Open AccessArticle

Next-Generation Sequencing of Chinese Children with Congenital Hearing Loss Reveals Rare and Novel Variants in Known and Candidate Genes

by Yuan Jin, Xiaozhou Liu, Qiong Zhang, Ying Xiong, Yao Hu, Haixia He, Wei Chen and Yu Sun

Biomedicines 2024, 12(12), 2657; https://doi.org/10.3390/biomedicines12122657 - 21 Nov 2024

Abstract

Background: Hearing loss (HL) is the most common disorder in newborns with a highly heterogeneous genetic background. Despite significant progress in screening and identifying genes related to congenital hearing loss, there are still candidate genes implicated in HL that remain undiscovered. Methods: We [...] Read more.

Background: Hearing loss (HL) is the most common disorder in newborns with a highly heterogeneous genetic background. Despite significant progress in screening and identifying genes related to congenital hearing loss, there are still candidate genes implicated in HL that remain undiscovered. Methods: We investigated HL in 43 Chinese families by segregating bilateral sensorineural HL via whole-exome sequencing (WES) and Sanger sequencing. Results: Variants were found in 10 known non-syndromic hearing loss (NSHL) genes, 5 known syndromic hearing loss (SHL) genes, and 1 candidate HL gene, ATP7B. RNA sequencing revealed ATP7B mRNA expression in developing and adult cochleae. The immunohistochemistry of the adult mouse cochlear tissue revealed the prominent expression of ATP7B in the organ of Corti and the spiral ganglion neuron. Overall, we propose a new candidate gene, ATP7B, for congenital hearing loss and novel variants in known HL genes, which expands our understanding of the etiology of HL. Conclusions: The next-generation sequencing could effectively improve the etiological diagnosis rate of congenital hearing loss in children. Full article

(This article belongs to the Section Molecular Genetics and Genetic Diseases)

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19 pages, 9365 KiB

Open AccessArticle

Integrative Multi-Omics Analysis Reveals Critical Molecular Networks Linking Intestinal-System Diseases to Colorectal Cancer Progression

by Shiliang Ji, Haoran Hu, Ruifang Zhu, Dongkai Guo, Yujing Liu, Yang Yang, Tian Li, Chen Zou, Yiguo Jiang and Guilai Liu

Biomedicines 2024, 12(12), 2656; https://doi.org/10.3390/biomedicines12122656 - 21 Nov 2024

Abstract

Background/Objectives: Colorectal cancer (CRC) frequently co-occurs with intestinal system diseases (ISDs), yet their molecular interplay remains poorly understood. We employed a comprehensive bioinformatics approach to elucidate shared genetic signatures and pathways between CRC and ISDs. Methods: We systematically analyzed 12 microarray [...] Read more.

Background/Objectives: Colorectal cancer (CRC) frequently co-occurs with intestinal system diseases (ISDs), yet their molecular interplay remains poorly understood. We employed a comprehensive bioinformatics approach to elucidate shared genetic signatures and pathways between CRC and ISDs. Methods: We systematically analyzed 12 microarray and RNA-seq datasets encompassing 989 samples across seven ISDs and CRC. Differentially expressed genes (DEGs) were identified using Limma and DESeq2. Functional enrichment analysis was performed using clusterProfiler. Protein–protein interaction networks were constructed via STRING and visualized with Cytoscape to identify hub genes. Clinical significance of shared genes was further assessed through survival analysis and validated by immunohistochemistry staining of 30 paired CRC–normal tissue samples. Results: Integrating bioinformatics and machine learning approaches, we uncovered 160 shared DEGs (87 upregulated, 73 downregulated), which predominantly enriched cell metabolism, immune homeostasis, gut–brain communication, and inflammation pathways. Network analysis revealed nine key hub proteins linking CRC and ISDs, with seven upregulated (CD44, MYC, IL17A, CXCL1, FCGR3A, SPP1, and IL1A) and two downregulated (CXCL12 and CCL5). Survival analysis demonstrated the prognostic potential of these shared genes, while immunohistochemistry confirmed their differential expression in CRC tissues. Conclusions: Our findings unveil potential biomarkers and therapeutic targets, providing insights into ISD-influenced CRC progression and offering a robust foundation for improved diagnostic and treatment strategies in ISD-associated CRC. Full article

(This article belongs to the Special Issue Genetic Research on Neuropsychiatric Disorders and Complex Human Diseases)

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26 pages, 703 KiB

Open AccessReview

The Importance of Genetic Screening on the Syndromes of Colorectal Cancer and Gastric Cancer: A 2024 Update

by Iulia Lupan, Ciprian Silaghi, Claudia Stroe, Adriana Muntean, Diana Deleanu, Vasile Bintintan and Gabriel Samasca

Biomedicines 2024, 12(12), 2655; https://doi.org/10.3390/biomedicines12122655 - 21 Nov 2024

Abstract

Gastrointestinal cancers (GIC), encompassing colonic, rectal, and gastric malignancies, rank among the most prevalent cancer types globally, contributing significantly to cancer-related mortality. In the scientific literature, various syndromes associated with colorectal and gastric cancers have been elucidated, highlighting the intricate interplay between genetic [...] Read more.

Gastrointestinal cancers (GIC), encompassing colonic, rectal, and gastric malignancies, rank among the most prevalent cancer types globally, contributing significantly to cancer-related mortality. In the scientific literature, various syndromes associated with colorectal and gastric cancers have been elucidated, highlighting the intricate interplay between genetic factors and disease manifestation. The primary objective of this study was to conduct a genetic exploration aimed at elucidating these associations and identifying shared genetic determinants across these cancer types. Notably, considerable research has focused on the KRAS gene mutations, polymorphisms in nucleic acids, the Wnt signaling pathway, and the role of chemokine ligands in tumorigenesis. While investigations into natural plant extracts as potential therapeutic agents are still in their nascent stages, they represent a promising avenue for future research. Ongoing studies are essential to uncover suitable biomarkers that could facilitate the identification and understanding of the genetic links between these GIC. This exploration not only seeks to enhance our comprehension of the underlying genetic architecture but also aims to inform the development of targeted therapies and preventive strategies. Full article

(This article belongs to the Special Issue Genetic Research on Colorectal Cancer)

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19 pages, 6575 KiB

Open AccessArticle

Chronic Sleep Deprivation Causes Anxiety, Depression and Impaired Gut Barrier in Female Mice—Correlation Analysis from Fecal Microbiome and Metabolome

by Lingyue Li, Zilin Meng, Yuebing Huang, Luyao Xu, Qianling Chen, Dongfang Qiao and Xia Yue

Biomedicines 2024, 12(12), 2654; https://doi.org/10.3390/biomedicines12122654 - 21 Nov 2024

Abstract

Background: Chronic sleep deprivation (CSD) plays an important role in mood disorders. However, the changes in the gut microbiota and metabolites associated with CSD-induced anxiety/depression-like behavior in female mice have not been determined. Due to the influence of endogenous hormone levels, females are [...] Read more.

Background: Chronic sleep deprivation (CSD) plays an important role in mood disorders. However, the changes in the gut microbiota and metabolites associated with CSD-induced anxiety/depression-like behavior in female mice have not been determined. Due to the influence of endogenous hormone levels, females are more susceptible than males to negative emotions caused by sleep deprivation. Here, we aim to investigate how CSD changes the gut microbiota and behavior and uncover the relationship between CSD and gut microbiota and its metabolites in female mice. Methods: We used a 48-day sleep deprivation (SD) model using the modified multiple platform method (MMPM) to induce anxiety/depression-like behavior in female C57BL/6J mice and verified our results using the open field test, elevated plus maze, novel object recognition test, forced swim test, and tail suspension test. We collected fecal samples of mice for 16S rDNA sequencing and untargeted metabolomic analysis and colons for histopathological observation. We used Spearmen analysis to find the correlations between differential bacterial taxa, fecal metabolites, and behaviors. Results: Our study demonstrates that CSD induced anxiety/depressive-like behaviors in female mice. The results of 16S rDNA sequencing suggested that the relative abundance of the harmful bacteria g_ Rothia, g_ Streptococcus, g_ Pantoea, and g_ Klebsiella were significantly increased, while the beneficial bacteria g_ Rikenella, g_ Eubacterium]-xylanophilum-group, and g_ Eisenbergiella were significantly decreased after SD. Glycerophospholipid metabolism and glutathione metabolism were identified as key pathways in the fecal metabolism related to oxidative stress and inflammatory states of the intestine. Histological observation showed hyperplasia of epithelial cells, a decrease in goblet cells, and glandular atrophy of the colon in SD mice. There were correlations between some of the differential bacterial taxa, fecal metabolites, and behaviors. Conclusion: In summary, we found that CSD induced anxiety/depression-like behavior, caused gut microbiota dysbiosis, altered fecal metabolism, and damaged the colon barrier in female mice. Full article

(This article belongs to the Section Endocrinology and Metabolism Research)

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20 pages, 15501 KiB

Open AccessArticle

Pan-Cancer Analysis Reveals the Potential of PLOD1 as a Prognostic and Immune Biomarker for Human Cancer

by Zhao Zhai, Shuo Wang, Yudong Cao, Jia Liu, Qiang Zhao, Yongpeng Ji, Xiao Yang, Xingxing Tang, Jinchao Ma and Peng Du

Biomedicines 2024, 12(12), 2653; https://doi.org/10.3390/biomedicines12122653 - 21 Nov 2024

Abstract

Background/Objectives: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is known as an enhancer of collagen fiber deposition and cross-linking stability. However, there is limited information on its function in tumors. In this study, we aimed to elucidate the function and potential mechanism of action of [...] Read more.

Background/Objectives: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is known as an enhancer of collagen fiber deposition and cross-linking stability. However, there is limited information on its function in tumors. In this study, we aimed to elucidate the function and potential mechanism of action of PLOD1 across cancers. Methods: We assessed the pan-cancer expression, mutation, methylation and prognostic value of PLOD1 through multiple online databases. In addition, we performed correlation analyses of its immunological features, as well as functional assessment analyses of PLOD1. Finally, we assessed the effect of PLOD1 knockdown on bladder tumor cells using in vitro experiments. Results: Our findings suggest that PLOD1 is aberrantly expressed in multiple cancer types, accompanied by a poor prognosis. Epigenetic alterations in PLOD1 are highly heterogeneous across a wide range of tumors, and aberrant methylation and copy number variants correlate with a poor prognosis. In the tumor microenvironment, PLOD1 expression correlated positively with the infiltration level of various immunosuppressive cells (e.g., monocytes, macrophages and tumor-associated fibroblasts) and negatively with immune-killing cells (e.g., CD8⁺ T cells, B cells and CD4⁺ T cells). In addition, PLOD1 expression was associated with immune checkpoints and immunomodulatory genes. Finally, in vitro experiments demonstrated that knockdown of PLOD1 reduced the proliferation, migration and antiapoptotic abilities of T24 cells. Conclusions: The results of this study demonstrate that PLOD1 is a potential oncogene and prognostic biomarker in pan-cancer; tumor tissues with high PLOD1 expression reveal a relatively immunosuppressive tumor microenvironment. Full article

(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)

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16 pages, 3274 KiB

Open AccessArticle

Evaluation of BRIP-1 (FANCJ) and FANCI Protein Expression in Ovarian Cancer Tissue

by Mateusz Kozłowski, Dominika Borzyszkowska, Anna Golara, Damian Durys, Katarzyna Piotrowska, Agnieszka Kempińska-Podhorodecka and Aneta Cymbaluk-Płoska

Biomedicines 2024, 12(12), 2652; https://doi.org/10.3390/biomedicines12122652 - 21 Nov 2024

Abstract

Background: Ovarian cancer is one of the most common cancers in women. Markers associated with ovarian cancer are still being sought. The aim of this study was to evaluate the expression of BRIP-1 (FANCJ) and FANCI proteins in ovarian cancer tissue and to [...] Read more.

Background: Ovarian cancer is one of the most common cancers in women. Markers associated with ovarian cancer are still being sought. The aim of this study was to evaluate the expression of BRIP-1 (FANCJ) and FANCI proteins in ovarian cancer tissue and to assess these expressions in differentiating the described clinical features. Methods: The study enrolled 68 patients with ovarian cancer. The cohort was divided into a HGSOC (high-grade serous ovarian cancer) group and a non-HGSOC group, which represented ovarian cancer other than HGSOC. Immunohistochemical evaluation of FANCI and BRIP-1 (FANCJ) protein expression in ovarian cancer tissue samples was performed. All statistical analyses were performed using StatView software (Carry, NC, USA). Results: The FANCI protein mostly showed moderate positive and strong positive expression, while BRIP-1 protein mostly showed no expression or positive expression. Patients with lower expression of FANCI and BRIP-1 showed differences in the clinical stage of HGSOC, which was not observed in patients with higher expression of these proteins. In addition, patients with lower BRIP-1 expression showed differences in menopausal status, which was not observed in patients with higher expression of this protein. Conclusions: This study shows that FANCI protein is a marker associated with lower FIGO stage and histologically high-grade cancer in a group of all ovarian cancers and in non-HGSOC. Full article

(This article belongs to the Special Issue Urogenital Cancers: New Molecular and Translational Aspects on Carcinogenesis and Treatments)

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21 pages, 1153 KiB

Open AccessArticle

Reference Interval for Glycated Albumin, 1,5-AG/GA, and GA/HbA1c Ratios and Cut-Off Values for Type 1, Type 2, and Gestational Diabetes: A Cross-Sectional Study

by Yusra Al-Lahham, Waldemar Volanski, Liana Signorini, Ademir Luiz do Prado, Glaucio Valdameri, Vivian Rotuno Moure, Marciane Welter, Alexessander C. Alves, Marcel Henrique Marcondes Sari, Fabiane Gomes de Moraes Rego and Geraldo Picheth

Biomedicines 2024, 12(12), 2651; https://doi.org/10.3390/biomedicines12122651 - 21 Nov 2024

Abstract

Background/Objectives: Glycated albumin (GA) serves as a biomarker for short-term glycemic control (2–3 weeks), playing a role in diabetes management. Our goal was to establish reference intervals (RIs) for serum GA, and the ratios of 1,5-anhydroglucitol to GA (AGI) and GA to HbA1c [...] Read more.

Background/Objectives: Glycated albumin (GA) serves as a biomarker for short-term glycemic control (2–3 weeks), playing a role in diabetes management. Our goal was to establish reference intervals (RIs) for serum GA, and the ratios of 1,5-anhydroglucitol to GA (AGI) and GA to HbA1c in a Euro-Brazilian pediatric population (10 y, n = 299), adults (43.5 y; n = 290), and pregnant women (26 y, n = 406; 26.5 ± 3.1 gestation weeks). Methods: Receiver operating characteristic curve analysis was employed to determine RIs for type 1 diabetes (T1D) in children (n = 148) and adults (n = 81), type 2 diabetes (T2D, n = 283), and gestational diabetes mellitus (GDM, n = 177). Results: Both non-pregnant and pregnant women exhibited GA RIs of 10.0–13.3% and 10.6–14.7%, respectively. The AGI ratio varied from 1.2–4.3 in children, 0.9–3.6 in adults, and 0.8–3.1 in pregnant women. Meanwhile, the GA/HbA1c ratio ranged from 1.8–2.6 in children and adults to 2.3–3.6 in pregnant women. GA and AGI ratios accurately differentiated between T1D and T2D, demonstrating high sensitivity (>84%) and specificity (>97%), with AGI showing superior performance (AUC > 0.99). The GA/HbA1c ratio exhibited moderate discriminatory power (AUC > 0.733) but was less effective in distinguishing adult-onset T1D and T2D, suggesting its limited utility in certain groups. Conclusions: The proposed RIs are consistent with those of other Caucasian populations, affirming their relevance for Euro-Brazilian patients. The GA and AGI ratios emerge as valuable diagnostic tools for T1D and T2D, though their reduced sensitivity in diagnosing GDM warrants further investigation. Clinicians might leverage GA and AGI ratios for more tailored diabetes management, especially when HbA1c results are not optimal. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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Graphical abstract

27 pages, 1692 KiB

Open AccessArticle

Drug-Induced Pulmonary Fibrosis: National Database Analysis

by Olga I. Butranova, Elizaveta N. Terekhina, Sergey K. Zyryanov, Geliia N. Gildeeva, Anna A. Abramova, Yury O. Kustov, Irina L. Asetskaya and Vitaly A. Polivanov

Biomedicines 2024, 12(12), 2650; https://doi.org/10.3390/biomedicines12122650 - 21 Nov 2024

Abstract

Background/Objectives: Pulmonary fibrosis (PF) results in a progressive decline of lung function due to scarring. Drugs are among the most common causes of PF. The objective of our study was to reveal the structure of drugs involved in PF development. Methods: we performed [...] Read more.

Background/Objectives: Pulmonary fibrosis (PF) results in a progressive decline of lung function due to scarring. Drugs are among the most common causes of PF. The objective of our study was to reveal the structure of drugs involved in PF development. Methods: we performed a retrospective descriptive pharmacoepidemiologic study on spontaneous reports (SRs) with data on PF registered in the Russian National Pharmacovigilance database for the period from 4 January 2019 to 31 May 2024. Results: A total of 1308 SRs on PF were finally identified with patients mean age of 59.3 ± 23.4 years. Death was reported in 30.7% (n = 401) with mean age of 59.9 ± 13.8 years. In the structure of culprit drugs, the following groups were leaders: antineoplastic and immunomodulating agents (51.9%); systemic hormonal preparations, excluding sex hormones and insulins (7.4%); drugs affecting nervous system (7.1%); respiratory system (7.1%); alimentary tract and metabolism (6.5%); and cardiovascular system (5.5%). In the total sample, the top ten drugs were rituximab (5.5%), methotrexate (4.4%), etanercept (4.2%), leflunomide (4.0%), adalimumab (3.7%), tocilizumab (3.3%), abatacept (3.0%), alendronic acid (2.7%), secukinumab (2.6%), and infliximab (2.4%). The number of SRs per year nearly doubled from 2021 to 2022 and from 2022 to 2023 with a maximum peak expected for 2024. Conclusions: Our study demonstrated increased reporting on PF in the National Pharmacovigilance database from 2019 to 2024. We revealed outstanding results for the role of antineoplastic and immunomodulating agents in PF development. Full article

(This article belongs to the Special Issue Biology of Fibroblasts and Fibrosis)

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