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Biomedicines
Volume 12
Issue 10
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Biomedicines, Volume 12, Issue 10 (October 2024) – 254 articles

Cover Story (view full-size image): Busulfan is an FDA-approved alkylating drug used in the chemotherapy of advanced acute myeloid leukemia. The precise mechanisms by which Busulfan kills spermatogonia stem cells (SSCs) are not yet completely understood. Using a murine model, we compared Busulfan-induced apoptosis between testis and ovary tissues. In the testis, the mRNA levels of TNF-α and TAF7 are downregulated, and testosterone levels are suppressed. We executed in situ hybridization and single-nuclei RNA sequencing, finding that less TAF7 mRNA is present in SSCs after chemotherapy. Thus, our data indicate a possible function of TAF7 in the regulation of SSCs and spermatogenesis following downregulation by Busulfan. These findings underlie the potential impact of Busulfan on cancer chemotherapy prognosis. View this paper
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14 pages, 2665 KiB  
Review
Chronically Increased Levels of Circulating Insulin Secondary to Insulin Resistance: A Silent Killer
by Serafino Fazio, Paolo Bellavite and Flora Affuso
Biomedicines 2024, 12(10), 2416; https://doi.org/10.3390/biomedicines12102416 - 21 Oct 2024
Viewed by 1691
Abstract
Despite all the progress made by science in the prevention and treatment of cardiovascular diseases and cancers, these are still the main reasons for hospitalizations and death in the Western world. Among the possible causes of this situation, disorders related to hyperinsulinemia and [...] Read more.
Despite all the progress made by science in the prevention and treatment of cardiovascular diseases and cancers, these are still the main reasons for hospitalizations and death in the Western world. Among the possible causes of this situation, disorders related to hyperinsulinemia and insulin resistance (Hyperin/IR) are still little-known topics. An analysis of the literature shows that this condition is a multiple risk factor for type 2 diabetes, cardiovascular diseases, cellular senescence and cancer, and neurodegenerative diseases. Hyperin/IR is progressively increasing worldwide, and its prevalence has now exceeded 50% of the general population and in overweight children. Asymptomatic or poorly symptomatic, it can last for many years before manifesting itself as diabetes, cardiovascular disease, neoplasm, cognitive deficit, or dementia, therefore leading to enormous social and healthcare costs. For these reasons, a screening plan for this pathology should be implemented for the purpose of identifying people with Hyperin/IR and promptly starting them on preventive treatment. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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17 pages, 1271 KiB  
Systematic Review
Towards Transforming Neurorehabilitation: The Impact of Artificial Intelligence on Diagnosis and Treatment of Neurological Disorders
by Andrea Calderone, Desiree Latella, Mirjam Bonanno, Angelo Quartarone, Sepehr Mojdehdehbaher, Antonio Celesti and Rocco Salvatore Calabrò
Biomedicines 2024, 12(10), 2415; https://doi.org/10.3390/biomedicines12102415 - 21 Oct 2024
Viewed by 1933
Abstract
Background and Objectives: Neurological disorders like stroke, spinal cord injury (SCI), and Parkinson’s disease (PD) significantly affect global health, requiring accurate diagnosis and long-term neurorehabilitation. Artificial intelligence (AI), such as machine learning (ML), may enhance early diagnosis, personalize treatment, and optimize rehabilitation through [...] Read more.
Background and Objectives: Neurological disorders like stroke, spinal cord injury (SCI), and Parkinson’s disease (PD) significantly affect global health, requiring accurate diagnosis and long-term neurorehabilitation. Artificial intelligence (AI), such as machine learning (ML), may enhance early diagnosis, personalize treatment, and optimize rehabilitation through predictive analytics, robotic systems, and brain-computer interfaces, improving outcomes for patients. This systematic review examines how AI and ML systems influence diagnosis and treatment in neurorehabilitation among neurological disorders. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, and Scopus databases with a search time range from 2014 to 2024. This review has been registered on Open OSF (n) EH9PT. Results: Recent advancements in AI and ML are revolutionizing motor rehabilitation and diagnosis for conditions like stroke, SCI, and PD, offering new opportunities for personalized care and improved outcomes. These technologies enhance clinical assessments, therapy personalization, and remote monitoring, providing more precise interventions and better long-term management. Conclusions: AI is revolutionizing neurorehabilitation, offering personalized, data-driven treatments that enhance recovery in neurological disorders. Future efforts should focus on large-scale validation, ethical considerations, and expanding access to advanced, home-based care. Full article
(This article belongs to the Special Issue Emerging Research in Neurorehabilitation)
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14 pages, 3211 KiB  
Article
Microvascular and Structural Characterization of Birdshot Chorioretinitis in Active and Inactive Phases
by Aina Moll-Udina, Marina Dotti-Boada, Anabel Rodríguez, Maite Sainz-de-la-Maza, Alfredo Adán and Victor Llorenç
Biomedicines 2024, 12(10), 2414; https://doi.org/10.3390/biomedicines12102414 - 21 Oct 2024
Viewed by 584
Abstract
Objective: This study aimed to examine microvascular changes and identify predictors of short-term quiescence in active birdshot chorioretinitis (BSCR). Methods: An observational, prospective, 12-month follow-up cohort study was conducted. BSCR eyes were clinically assessed at baseline, categorized as active or inactive, and reevaluated [...] Read more.
Objective: This study aimed to examine microvascular changes and identify predictors of short-term quiescence in active birdshot chorioretinitis (BSCR). Methods: An observational, prospective, 12-month follow-up cohort study was conducted. BSCR eyes were clinically assessed at baseline, categorized as active or inactive, and reevaluated at 12 months. Based on their clinical activity at both timepoints, eyes were divided into three subgroups: active-to-inactive (A-I), consistently active (A-A), and consistently inactive (I-I). Structural OCT, OCT-angiography (OCT-A), and ultra-widefield imaging were utilized. Exam data from fundus and nasal subfields were analyzed for microvascular changes and quiescence predictors. Results: Sixty eyes from 30 BSCR patients (47% women, 53% men, mean age 59.7 ± 12.3 years) were included. In the A-I group (16 eyes), vascular density and perfusion indices increased in all subfields post-quiescence, contrasting with the other groups. Perifoveal looping in the superficial capillary plexus predicted quiescence at 12 months compared with the A-A group. Conclusions: Vascular density rises after complete inflammation control in BSCR, and perifoveal capillary loops serve as potential predictors of short-term quiescence in active BSCR. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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13 pages, 2741 KiB  
Article
Endothelial Biomarkers Are Superior to Classic Inflammatory Biomarkers in Community-Acquired Pneumonia
by Paula González-Jiménez, Mónica Piqueras, Ana Latorre, Jordi Tortosa-Carreres, Noé Mengot, Ricardo Alonso, Soledad Reyes, Isabel Amara-Elori, Luis Martínez-Dolz, Antonio Moscardó, Rosario Menéndez and Raúl Méndez
Biomedicines 2024, 12(10), 2413; https://doi.org/10.3390/biomedicines12102413 - 21 Oct 2024
Viewed by 624
Abstract
Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to [...] Read more.
Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP. Full article
(This article belongs to the Special Issue Neutrophils, Fast and Strong 2.0)
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22 pages, 5657 KiB  
Systematic Review
“Hands-On” and “Hands-Off” Physiotherapy Treatments in Fibromyalgia Patients: A Systematic Review and Meta-Analysis
by Riccardo Buraschi, Giorgia Ranica, Jorge Hugo Villafañe, Rosa Pullara, Massimiliano Gobbo and Joel Pollet
Biomedicines 2024, 12(10), 2412; https://doi.org/10.3390/biomedicines12102412 - 21 Oct 2024
Viewed by 929
Abstract
Background: Physiotherapy plays a key role in managing fibromyalgia, a multifaceted disorder, through a combination of active and passive treatments. The purpose of this review is to compare the efficacy of “hands-off” treatments alone versus the combination of “hands-off” and “hands-on” therapies. [...] Read more.
Background: Physiotherapy plays a key role in managing fibromyalgia, a multifaceted disorder, through a combination of active and passive treatments. The purpose of this review is to compare the efficacy of “hands-off” treatments alone versus the combination of “hands-off” and “hands-on” therapies. Methods: MEDLINE (PubMed), CENTRAL, and Embase were searched. English-language randomized controlled trials involving adults with fibromyalgia were included. The included studies were divided into subgroups to reduce the possible heterogeneity. We calculated the standardized mean difference or mean difference with 95% confidence intervals for the continuous data according to the outcome measures. We used the risk ratio for dichotomous data of the drop-out rate of the studies. Results: We included and analyzed seven RCTs. The meta-analysis showed no significant results in the outcomes, pain, QoL, health status, and drop-out rate. We found significant results (p < 0.001) in favor of combining “hands-off” and “hands-on” treatments for the rest quality (SMD 0.72, 95% CI 0.35 to 1.09). Conclusions: This review increases the treatment options available for clinicians. Up to now, the main guidelines on managing fibromyalgia suggest only approaches based on “hands-off” treatments. These findings suggest that other approaches based on mixed interventions combining “hands-off” and “hands-on” treatments did not reduce the patient outcomes. Moreover, the mixed intervention led to better results for the patients’ sleep quality than the “hands-off” treatments alone. Full article
(This article belongs to the Special Issue Advanced Research on Fibromyalgia (2nd Edition))
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15 pages, 1729 KiB  
Article
Demographic Characteristics and Survival in Young-Onset Colorectal Neuroendocrine Neoplasms
by Deepak Vadehra, Sahithi Sonti, Beas Siromoni, Mrinalini Ramesh, Debduti Mukhopadhyay, Adrienne Groman, Renuka Iyer and Sarbajit Mukherjee
Biomedicines 2024, 12(10), 2411; https://doi.org/10.3390/biomedicines12102411 - 21 Oct 2024
Viewed by 703
Abstract
Background/Objectives: Recent epidemiological studies have revealed an upward trend in young-onset colorectal cancer (YOCRC) overall, whereas specific data on young-onset colorectal neuroendocrine neoplasms (YONEN) remain limited. This study investigated the demographic characteristics and survival trends in YONEN and compared these with those of [...] Read more.
Background/Objectives: Recent epidemiological studies have revealed an upward trend in young-onset colorectal cancer (YOCRC) overall, whereas specific data on young-onset colorectal neuroendocrine neoplasms (YONEN) remain limited. This study investigated the demographic characteristics and survival trends in YONEN and compared these with those of young-onset colorectal adenocarcinoma (YOADC), the most common histologic subtype of YOCRC. Methods: A retrospective analysis was conducted from 2000 to 2019 using the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were assessed using univariate and multivariable Cox proportional models, with demographic differences evaluated via Wilcoxon rank sum and Chi-square tests. Results: Out of 61,705 patients aged 20–49 with colorectal cancer, 8% had NEN, and 92% had adenocarcinoma. The YONEN cohort had a higher proportion of Black patients and a lower proportion of White patients than the YOADC cohort (21% vs. 13% and 44% vs. 57%, respectively). NEN was more commonly found in the rectum (79%), and adenocarcinoma was mostly colonic (57%) in origin. YONEN patients had better survival than YOADC patients. Multivariate analysis in YONEN patients revealed that Hispanic patients had better overall survival compared to White patients (HR 0.67, 95% CI 0.47–0.95, p = 0.024). Conclusions: Racial disparities should be investigated further to aid in policymaking and targeted interventions. Full article
(This article belongs to the Special Issue Recent Advances in Gastrointestinal Cancers: From Microbiota Modulation to New Therapeutic Approaches)
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15 pages, 3971 KiB  
Article
Effects of Angiotensin-I-Converting Enzyme (ACE) Mutations Associated with Alzheimer’s Disease on Blood ACE Phenotype
by Olga V. Kryukova, Igor O. Islanov, Elena V. Zaklyazminskaya, Dmitry O. Korostin, Vera A. Belova, Valery V. Cheranev, Zhanna A. Repinskaia, Svetlana A. Tonevitskaya, Pavel A. Petukhov, Steven M. Dudek, Olga A. Kost, Denis V. Rebrikov and Sergei M. Danilov
Biomedicines 2024, 12(10), 2410; https://doi.org/10.3390/biomedicines12102410 - 21 Oct 2024
Viewed by 682
Abstract
Backgrounds. Our recent analysis of 1200+ existing missense ACE mutations revealed that 400+ mutations are damaging and led us to hypothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of [...] Read more.
Backgrounds. Our recent analysis of 1200+ existing missense ACE mutations revealed that 400+ mutations are damaging and led us to hypothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer’s disease (AD). Methods. Here, we quantified blood ACE levels in EDTA plasma from 41 subjects with 10 different heterozygous ACE mutations, as well as 33 controls, and estimated the effect of these mutations on ACE phenotype using a set of mAbs to ACE and two ACE substrates. Results. We found that relatively frequent (~1%) AD-associated ACE mutations in the N domain of ACE, Y215C, and G325R are truly damaging and likely transport-deficient, with the ACE levels in plasma at only ~50% of controls. Another AD-associated ACE mutation, R1250Q, in the cytoplasmic tail, did not cause a decrease in ACE and likely did not affect surface ACE expression. We have also developed a method to identify patients with anti-catalytic mutations in the N domain. These mutations may result in reduced degradation of amyloid beta peptide Aβ42, an important component for amyloid deposition. Consequently, these could pose a risk factor for the development of AD. Conclusions. Therefore, a systematic analysis of blood ACE levels in patients with all ACE mutations has the potential to identify individuals at an increased risk of late-onset AD. These individuals may benefit from future preventive or therapeutic interventions involving a combination of chemical and pharmacological chaperones, as well as proteasome inhibitors, aiming to enhance ACE protein traffic. This approach has been previously demonstrated in our cell model of the transport-deficient ACE mutation Q1069R. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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14 pages, 6520 KiB  
Article
Skin Microbiota, Immune Cell, and Skin Fibrosis: A Comprehensive Mendelian Randomization Study
by Zirui Zhao, Yanchao Rong, Rong Yin, Ruixi Zeng, Zhongye Xu, Dongming Lv, Zhicheng Hu, Xiaoling Cao and Bing Tang
Biomedicines 2024, 12(10), 2409; https://doi.org/10.3390/biomedicines12102409 - 21 Oct 2024
Viewed by 767
Abstract
Background: Microbiota dysbiosis has been reported to lead to leaky epithelia and trigger numerous dermatological conditions. However, potential causal associations between skin microbiota and skin fibrosis and whether immune cells act as mediators remain unclear. Methods: Summary statistics of skin microbiota, immune cells, [...] Read more.
Background: Microbiota dysbiosis has been reported to lead to leaky epithelia and trigger numerous dermatological conditions. However, potential causal associations between skin microbiota and skin fibrosis and whether immune cells act as mediators remain unclear. Methods: Summary statistics of skin microbiota, immune cells, and skin fibrosis were identified from large-scale genome-wide association studies summary data. Bidirectional Mendelian randomization was performed to ascertain unidirectional causal effects between skin microbiota, immune cells, and skin fibrosis. We performed a mediation analysis to identify the role of immune cells in the pathway from skin microbiota to skin fibrosis. Results: Three specific skin microbiotas were positively associated with skin fibrosis, while the other three were negative. A total of 15 immune cell traits were associated with increased skin fibrosis risk, while 27 were associated with a decreased risk. Moreover, two immune cell traits were identified as mediating factors. Conclusions: Causal associations were identified between skin microbiota, immune cells, and skin fibrosis. There is evidence that immune cells exert mediating effects on skin microbiota in skin fibrosis. In addition, some strains exhibit different effects on skin fibrosis in distinct environments. Full article
(This article belongs to the Special Issue The Interplay between Immunity and Microbiota in Human Health and Diseases (2nd Edition))
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17 pages, 1689 KiB  
Review
The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy
by Bahejuan Jiaerken, Wei Liu, Jiaojiao Zheng, Weifeng Qu, Qiao Wu and Zhilong Ai
Biomedicines 2024, 12(10), 2408; https://doi.org/10.3390/biomedicines12102408 - 21 Oct 2024
Viewed by 849
Abstract
(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key [...] Read more.
(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key biological functions in thyroid cancer. We discuss the multifaceted roles of SUMOylation in DNA repair mechanisms, protein stability, and the modulation of receptor activities, particularly in the context of thyroid cancer. (3) Results: The aberrant SUMOylation machinery contributes to tumorigenesis through altered gene expression and immune evasion mechanisms. Furthermore, we examine the therapeutic potential of targeting SUMOylation pathways in thyroid cancer treatment, emphasizing the need for further research to develop effective SUMOylation inhibitors. (4) Conclusions: By understanding the intricate roles of SUMOylation in cancer biology, we can pave the way for innovative therapeutic strategies to improve outcomes for patients with advanced tumors. Full article
(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)
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8 pages, 1342 KiB  
Brief Report
A Pilot Study of the Role of Semaphorin 4A (sema4A) and 3C (sema3C) in Non-Muscle-Invasive Bladder Cancer (NMIBC)
by Piotr Purpurowicz, Tomasz W. Kaminski, Władysław Kordan, Anna Korzekwa, Zbigniew Purpurowicz and Zbigniew Jabłonowski
Biomedicines 2024, 12(10), 2407; https://doi.org/10.3390/biomedicines12102407 - 21 Oct 2024
Viewed by 745
Abstract
Background/Objectives: Bladder cancer is a very important issue in contemporary urology. The aim of this pilot study was to assess for the first time the clinical utility of semaphorin 3C (sema3C) and 4A (sema4A) in patients with non-muscle-invasive bladder cancer (NMIBC). Methods: The [...] Read more.
Background/Objectives: Bladder cancer is a very important issue in contemporary urology. The aim of this pilot study was to assess for the first time the clinical utility of semaphorin 3C (sema3C) and 4A (sema4A) in patients with non-muscle-invasive bladder cancer (NMIBC). Methods: The experiment involved 15 patients with NMIBC and 5 patients without malignancies as the control group. Plasma and urinary concentrations of sema3C and sema4A were assessed by using an enzyme-linked immunosorbent assay (ELISA). Urinary sema4A concentration was below the detection level. Results: There was no statistically significant difference between patients and controls in terms of plasma sema4A and sema3C or urinary sema3C concentrations (p > 0.05). There was a significantly higher sema3C plasma concentration in patients with low-grade tumors (p = 0.0132) and an upward trend in sema4A plasma concentration for the subjects with Ta-stage tumors. Urinary sema3C concentration positively correlated with tumor size (R = 0.57, p = 0.03). Plasma sema3C concentration correlated negatively with tumor grade (R = −0.62, p = 0.01). Conclusions: Urinary sema4A concentration, which is below the detection threshold, is unlikely to be useful as a marker of NMIBC. Plasma sema4A concentration and sema3C concentration in plasma and urine cannot be used as stand-alone markers of NMIBC at this point. The plasma concentration of sema3C can potentially be considered in the future as a marker for tumors of lower grades. Plasma sema4A concentration could potentially be considered in the future as a marker for tumors of earlier stages. All of these observations are preliminary, so they have to be assessed in larger cohorts to make reliable recommendations. Nevertheless, our study lays the groundwork for further research to develop potential tests that could be used in daily practice to monitor and predict the course of cancer. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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23 pages, 2418 KiB  
Protocol
Collection, Establishment and Assessment of Complex Human Osteocartilaginous Explants for Modeling Osteoarthritis
by Camelia-Mihaela Danceanu-Zara, Adriana Petrovici, Luminita Labusca, Anca Emanuela Minuti, Cristina Stavila, Petru Plamadeala, Crina Elena Tiron, Dragoş Aniţă, Adriana Aniţă and Nicoleta Lupu
Biomedicines 2024, 12(10), 2406; https://doi.org/10.3390/biomedicines12102406 - 21 Oct 2024
Viewed by 600
Abstract
With the increasing burden of osteoarthritis worldwide, cost efficient and reliable models are needed to enable the development of innovative therapies or therapeutic interventions. Ex vivo models have been identified as valuable modalities in translational research, bridging the gap between in vitro and [...] Read more.
With the increasing burden of osteoarthritis worldwide, cost efficient and reliable models are needed to enable the development of innovative therapies or therapeutic interventions. Ex vivo models have been identified as valuable modalities in translational research, bridging the gap between in vitro and in vivo models. Osteocartilaginous explants from Osteoarthritis (OA) patients offer an exquisite opportunity for studying OA progression and testing novel therapies. We describe the protocol for establishing human osteocartilaginous explants with or without co-culture of homologous synovial tissue. Furthermore, a detailed protocol for the assessment of explanted tissue in terms of protein content using Western blot and immunohistochemistry is provided. Commentaries regarding the technique of choice, possible variations and expected results are inserted. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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21 pages, 2693 KiB  
Review
Apigenin as a Promising Agent for Enhancing Female Reproductive Function and Treating Associated Disorders
by Alexander V. Sirotkin and Abdel Halim Harrath
Biomedicines 2024, 12(10), 2405; https://doi.org/10.3390/biomedicines12102405 - 21 Oct 2024
Viewed by 943
Abstract
Apigenin is an organic flavonoid abundant in some plants such as parsley, chamomile, or celery. Recently, it has been investigated for several of its pharmacological characteristics, such as its ability to act as an antioxidant, reduce inflammation, and inhibit the growth of cancer [...] Read more.
Apigenin is an organic flavonoid abundant in some plants such as parsley, chamomile, or celery. Recently, it has been investigated for several of its pharmacological characteristics, such as its ability to act as an antioxidant, reduce inflammation, and inhibit the growth of cancer cells. The purpose of this review is to provide a summary of the existing knowledge regarding the effects of apigenin on female reproductive systems and its dysfunctions. Apigenin can influence reproductive processes by regulating multiple biological events, including oxidative processes, cell proliferation, apoptosis, cell renewal and viability, ovarian blood supply, and the release of reproductive hormones. It could stimulate ovarian folliculogenesis, as well as ovarian and embryonal cell proliferation and viability, which can lead to an increase in fertility and influence the release of reproductive hormones, which may exert its effects on female reproductive health. Furthermore, apigenin could inhibit the activities of ovarian cancer cells and alleviate the pathological changes in the female reproductive system caused by environmental pollutants, harmful medications, cancer, polycystic ovarian syndrome, ischemia, as well as endometriosis. Therefore, apigenin may have potential as a biostimulator for female reproductive processes and as a therapeutic agent for certain reproductive diseases. Full article
(This article belongs to the Special Issue Advanced Research in Early Pregnancy Loss and Other Pregnancy Complications)
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12 pages, 1377 KiB  
Article
miRNA in Machine-Learning-Based Diagnostics of Oral Cancer
by Xinghang Li, Valentina L. Kouznetsova and Igor F. Tsigelny
Biomedicines 2024, 12(10), 2404; https://doi.org/10.3390/biomedicines12102404 - 21 Oct 2024
Viewed by 785
Abstract
Background: MicroRNAs (miRNAs) are crucial regulators of gene expression, playing significant roles in various cellular processes, including cancer pathogenesis. Traditional cancer diagnostic methods, such as biopsies and histopathological analyses, while effective, are invasive, costly, and require specialized skills. With the rising global incidence [...] Read more.
Background: MicroRNAs (miRNAs) are crucial regulators of gene expression, playing significant roles in various cellular processes, including cancer pathogenesis. Traditional cancer diagnostic methods, such as biopsies and histopathological analyses, while effective, are invasive, costly, and require specialized skills. With the rising global incidence of cancer, there is a pressing need for more accessible and less invasive diagnostic alternatives. Objective: This research investigates the potential of machine-learning (ML) models based on miRNA attributes as non-invasive diagnostic tools for oral cancer. Methods and Tools: We utilized a comprehensive methodological framework involving the generation of miRNA attributes, including sequence characteristics, target gene associations, and cancer-specific signaling pathways. Results: The miRNAs were classified using various ML algorithms, with the BayesNet classifier demonstrating superior performance, achieving an accuracy of 95% and an area under receiver operating characteristic curve (AUC) of 0.98 during cross-validation. The model’s effectiveness was further validated using independent datasets, confirming its potential clinical utility. Discussion: Our findings highlight the promise of miRNA-based ML models in enhancing early cancer detection, reducing healthcare burdens, and potentially saving lives. Conclusions: This study paves the way for future research into miRNA biomarkers, offering a scalable and adaptable diagnostic approach for various cancers. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
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13 pages, 2654 KiB  
Communication
Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
by Alexey S. Kononikhin, Natalia L. Starodubtseva, Alexander G. Brzhozovskiy, Alisa O. Tokareva, Daria N. Kashirina, Natalia V. Zakharova, Anna E. Bugrova, Maria I. Indeykina, Liudmila Kh. Pastushkova, Irina M. Larina, Vladimir A. Mitkevich, Alexander A. Makarov and Evgeny N. Nikolaev
Biomedicines 2024, 12(10), 2403; https://doi.org/10.3390/biomedicines12102403 - 21 Oct 2024
Viewed by 922
Abstract
Background/Objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in [...] Read more.
Background/Objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer’s disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). Conclusions: The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels. Full article
(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)
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12 pages, 2685 KiB  
Article
Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning
by Yuxin Nie, Liyu Lin, Qiang Yang, Jiachang Hu, Minmin Sun, Fangfang Xiang, Xuesen Cao, Jinbo Yu, Yaqiong Wang, Jie Teng, Xiaoqiang Ding, Bo Shen and Zhen Zhang
Biomedicines 2024, 12(10), 2402; https://doi.org/10.3390/biomedicines12102402 - 20 Oct 2024
Viewed by 593
Abstract
Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K+) and calcium (Ca2+) [...] Read more.
Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K+) and calcium (Ca2+) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoKATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoKATP channel modulators were evaluated by administering diazoxide (DZX), a mitoKATP opener, and 5-hydroxydecanoate (5-HD), a mitoKATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca2+ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K+ and Ca2+ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoKATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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16 pages, 5163 KiB  
Review
Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment
by Benjamin M. Liu and A. Wallace Hayes
Biomedicines 2024, 12(10), 2401; https://doi.org/10.3390/biomedicines12102401 - 20 Oct 2024
Viewed by 772
Abstract
Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles [...] Read more.
Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles TiO2 and CuO, induce genotoxicity via direct DNA damage and/or reactive oxygen species-mediated indirect DNA damage. There are various physical features of MENMs that may play an important role in promoting their genotoxicity, for example, size and chemical composition. For a valid genotoxicity assessment of MENMs, general considerations should be given to various factors, including, but not limited to, NM characterization, sample preparation, dosing selection, NM cellular uptake, and metabolic activation. The recommended in vitro genotoxicity assays of MENMs include hprt gene mutation assay, chromosomal aberration assay, and micronucleus assay. However, there are still knowledge gaps in understanding the mechanisms underlying the genotoxicity of MENMs. There are also a variety of challenges in the utilization and interpretation of the genotoxicity assessment assays of MENMs. In this review article, we provide mechanistic insights into the genotoxicity of MENMs in the human environment. We review advances in applying new endpoints, biomarkers, and methods to the genotoxicity assessments of MENMs. The guidance of the United States, the United Kingdom, and the European Union on the genotoxicity assessments of MENMs is also discussed. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
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25 pages, 299 KiB  
Article
Hepatitis C Infection Is Not a Cardiovascular Risk Factor in Young Adults
by Paweł Rajewski, Małgorzata Pawłowska, Dorota Kozielewicz, Dorota Dybowska, Anita Olczak and Jakub Cieściński
Biomedicines 2024, 12(10), 2400; https://doi.org/10.3390/biomedicines12102400 - 20 Oct 2024
Viewed by 785
Abstract
Background: Cardiovascular diseases are one of the leading causes of hospitalization and death in Poland and around the world and are still an ongoing problem for modern medicine. Despite advances in diagnosis and treatment, both conservative and invasive, the prevention of cardiovascular [...] Read more.
Background: Cardiovascular diseases are one of the leading causes of hospitalization and death in Poland and around the world and are still an ongoing problem for modern medicine. Despite advances in diagnosis and treatment, both conservative and invasive, the prevention of cardiovascular disease directed at reducing risk factors remains a problem. The main classical risk factors for the development of cardiovascular disease in Poland include hypertension, lipid disorders, obesity, diabetes and smoking. A new non-classical risk factor is HCV infection. Most of the studies on the impact of HCV infection on cardiovascular disease involve elderly populations with long-term infections and advanced liver fibrosis. Methods: Hence, we set out to analyze the prevalence of risk factors and cardiovascular disease in a population of young adults under 45 years of age infected with HCV, according to gender, HCV genotype and the duration of infection. The study group consisted of 217 patients of both sexes aged 21 to 45 years (mean age 36 years). Results: No cardiovascular disease was found among the young adults infected with HCV in the study group. The most common risk factor was cigarette smoking, which affected 20.7% of the subjects, followed by hypertension (12%) and diabetes mellitus (5.5%); the prevalence was lower than in the general population. Most of the patients were characterized as overweight, with a mean BMI of 26.39 kg/m2. The mean values of other metabolic parameters—total cholesterol, LDL, HDL, uric acid and glucose—were within the population norm. The mean value of CRP was 1.43, which may indicate a moderate cardiovascular risk. Conclusions: Based on the conducted research, it was found that HCV infection in young individuals was not a risk factor for cardiovascular diseases, and the prevalence of risk factors was similar to that in the general population. The effect of HCV on the increase in C-reactive protein requires further study. The early detection of HCV infection and treatment can be considered as a prevention of cardiovascular disease. Full article
(This article belongs to the Special Issue Cardiac and Vascular Diseases: Pathogenesis, Pharmacological Treatments, Advances in Therapies (2nd Edition))
21 pages, 4467 KiB  
Article
The Generation of ROS by Exposure to Trihalomethanes Promotes the IκBα/NF-κB/p65 Complex Dissociation in Human Lung Fibroblast
by Minerva Nájera-Martínez, Israel Lara-Vega, Jhonatan Avilez-Alvarado, Nataraj S. Pagadala, Ricardo Dzul-Caamal, María Lilia Domínguez-López, Jack Tuszynski and Armando Vega-López
Biomedicines 2024, 12(10), 2399; https://doi.org/10.3390/biomedicines12102399 - 20 Oct 2024
Viewed by 864
Abstract
Background: Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CH2Cl2, CHCl3, and BrCHCl2, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and [...] Read more.
Background: Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CH2Cl2, CHCl3, and BrCHCl2, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) modulate these damages through their biotransformation processes, potentially generating toxic metabolites. However, the role of the oxidative stress response in cellular hyperproliferation, modulated by nuclear factor-kappa B (NF-κB), remains unclear. Methods: In this study, MRC-5 cells were treated with these compounds to evaluate reactive oxygen species (ROS) production, lipid peroxidation, phospho-NF-κB/p65 (Ser536) levels, and the activities of SOD, CAT, and GPx. Additionally, the interactions between HMs and ROS with the IκBα/NF-κB/p65 complex were analyzed using molecular docking. Results: Correlation analysis among biomarkers revealed positive relationships between pro-oxidant damage and antioxidant responses, particularly in cells treated with CH2Cl2 and BrCHCl2. Conversely, negative relationships were observed between ROS levels and NF-κB/p65 levels in cells treated with CH2Cl2 and CHCl3. The estimated relative free energy of binding using thermodynamic integration with the p65 subunit of NF-κB was −3.3 kcal/mol for BrCHCl2, −3.5 kcal/mol for both CHCl3 and O2•, and −3.6 kcal/mol for H2O2. Conclusions: Chloride and bromide atoms were found in close contact with IPT domain residues, particularly in the RHD region involved in DNA binding. Ser281 is located within this domain, facilitating the phosphorylation of this protein. Similarly, both ROS interacted with the IPT domain in the RHD region, with H2O2 forming a side-chain oxygen interaction with Leu280 adjacent to the phosphorylation site of p65. However, the negative correlation between ROS and phospho-NF-κB/p65 suggests that steric hindrance by ROS on the C-terminal domain of NF-κB/p65 may play a role in the antioxidant response. Full article
(This article belongs to the Special Issue Fibroblasts: Insights from Molecular and Pathophysiology Perspectives)
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21 pages, 2792 KiB  
Article
Three-Dimensional Model Analysis Revealed Differential Cytotoxic Effects of the NK-92 Cell Line and Primary NK Cells on Breast and Ovarian Carcinoma Cell Lines Mediated by Variations in Receptor–Ligand Interactions and Soluble Factor Profiles
by Nadezhda A. Alekseeva, Anna A. Boyko, Marina A. Shevchenko, Maria V. Grechikhina, Maria A. Streltsova, Ludmila G. Alekseeva, Alexander M. Sapozhnikov, Sergey M. Deyev and Elena I. Kovalenko
Biomedicines 2024, 12(10), 2398; https://doi.org/10.3390/biomedicines12102398 - 20 Oct 2024
Viewed by 807
Abstract
Background/objectives: The functional activity of a certain tumor determines the effectiveness of primary NK cells and NK-92 cell line-based cancer therapy; their therapeutic effectiveness against different tumors can vary. This work provides a direct simultaneous comparison of the cytotoxic effects of in vitro-activated [...] Read more.
Background/objectives: The functional activity of a certain tumor determines the effectiveness of primary NK cells and NK-92 cell line-based cancer therapy; their therapeutic effectiveness against different tumors can vary. This work provides a direct simultaneous comparison of the cytotoxic effects of in vitro-activated peripheral NK (pNK) cells and NK-92 cells in spheroid models of BT-474, MCF7 and SKOV-3 carcinomas and uncovers the reasons for the differential effectiveness of NK cells against tumors. Methods: Tumor spheroids of similar size and shape, obtained from agarose molds, were incubated with NK-92 or pNK cells for 24 h. Tumor cell death was detected using flow cytometry or confocal microscopy. Cytokine production, granzyme B levels and NK cell degranulation analyses were performed, along with pNK and target-cell phenotypic characterization. Results: While NK-92 and pNK cells lysed BT-474 spheroids with comparably low efficiency, pNK cells were more capable of eliminating MCF7 and SKOV-3 spheroids than NK-92 cells were. The results of the functional and phenotypic analyses strongly support the participation of the NKG2D-NKG2DL pathway in pNK cell activation induced by the most sensitive cytotoxic attack on SKOV-3 spheroids, whereas the CX3CR1-CX3CL1 axis appears to be involved in the pNK reaction against MCF-7 spheroids. Conclusions: We provide a new approach for the preliminary identification of the most promising NK cell receptors that can alter the effectiveness of cancer therapy depending on the specific tumor type. Using this approach, NK-92 cells or pNK subsets can be selected for further accumulation and/or genetic modification to improve specificity and reactivity. Full article
(This article belongs to the Special Issue The Role of NK Cells in Health and Diseases)
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13 pages, 4837 KiB  
Article
Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma
by Florian Weber, Kirsten Utpatel, Katja Evert, Thomas S. Weiss and Christa Buechler
Biomedicines 2024, 12(10), 2397; https://doi.org/10.3390/biomedicines12102397 - 19 Oct 2024
Viewed by 882
Abstract
Background/Objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels [...] Read more.
Background/Objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Methods: Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. Results: In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. Conclusions: In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging. Full article
(This article belongs to the Special Issue New Challenges in the Study of Liver Diseases: From Molecular Pathogenesis to Therapeutic Approaches—the 3rd Edition)
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12 pages, 11253 KiB  
Article
Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the ATXN2 Gene
by Anna Dorohova, Oksana Lyasota, Stepan Dzhimak, Alexandr Svidlov, Olga Leontyeva and Mikhail Drobotenko
Biomedicines 2024, 12(10), 2396; https://doi.org/10.3390/biomedicines12102396 - 19 Oct 2024
Viewed by 842
Abstract
Background: Trinucleotide repeats are the cause of many neurodegenerative diseases that are currently incurable. In this regard, the question of the causes of occurrence and methods of prevention or treatment of diseases caused by the expansion of repeats in the CAG tract of [...] Read more.
Background: Trinucleotide repeats are the cause of many neurodegenerative diseases that are currently incurable. In this regard, the question of the causes of occurrence and methods of prevention or treatment of diseases caused by the expansion of repeats in the CAG tract of the ATXN2 gene remains relevant. Previously, it was shown that the frequency of occurrence of additional OS (open states) zones increases with increasing length of the CAG tract, and the value inverse to the frequency correlates with the age of disease onset. Methods: In this work, the influence of the viscosity of the medium and the external torque on the stability of the CAG tract in the ATXN2 gene was studied using mathematical modeling methods. Results: It has been established that the probability of the appearance of additional OS zones of significant size increases with an increase in the CAG of the tract (k > 40 CAG repeats) for all viscosity values, however, at k ≤ 40, the change in viscosity does not significantly affect the probability of additional OS zones in the tract. Conclusions: It was found that under normal conditions (absence of pathology), viscosity does not have a reliable effect on the stability of the DNA molecule, but when pathology appears, an increase in viscosity contributes to an increase in DNA stability, and, accordingly, a decrease has a negative effect on the stabilization of the DNA molecule. In the zone of close to incomplete penetrance of the disease, viscosity does not have a reliable effect on the stability of the CAG tract. Full article
(This article belongs to the Special Issue Neurodegenerative Diseases: From Mechanisms to Therapeutic Approaches)
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10 pages, 2090 KiB  
Article
The Clinical and Sonographic Features of Cervical Muscle Involvement in Patients with Frozen Shoulder: A Retrospective Study
by Alice Chu-Wen Tang, Shih-Ting Huang, Szu-Yuan Wu and Simon Fuk-Tan Tang
Biomedicines 2024, 12(10), 2395; https://doi.org/10.3390/biomedicines12102395 - 19 Oct 2024
Viewed by 885
Abstract
Background/Objectives: Frozen shoulder is a common shoulder disorder that often places limitations on the range of motion of the shoulder. The disease may induce neck pain due to overuse of the neck muscle in an attempt to compensate for lack of shoulder [...] Read more.
Background/Objectives: Frozen shoulder is a common shoulder disorder that often places limitations on the range of motion of the shoulder. The disease may induce neck pain due to overuse of the neck muscle in an attempt to compensate for lack of shoulder movement. In clinical practice, swelling and inflammation of the scalene and levator scapulae may be detected via sonography in patients with frozen shoulder. The aim of this study was, therefore, to determine whether the involvement of the scalene complex or levator scapulae could compensate for the limited motion of the shoulder in patients with frozen shoulder. Methods: We retrospectively reviewed the medical records of 362 patients with unilateral frozen shoulder. These patients were divided into four groups depending on the involvement of the scalene complex or levator scapulae muscle. The range of motion of the shoulder—encompassing flexion, abduction, and external rotation—was measured with a goniometer. We also performed an ultrasound scan on each shoulder. The involvement of the scalene complex and levator scapulae muscle was also assessed via musculoskeletal ultrasound. Results: The range of motion of the shoulder in terms of flexion, abduction, external rotation, and total range of motion differed significantly between the four groups (p < 0.05). Patients in whom the scalene complex or levator scapulae muscle was involved demonstrated a significantly wider range of motion in different shoulder directions than patients without the involvement of those muscles (p < 0.05). Conclusions: A greater range of motion in the shoulder can be obtained through the activation of the scalene complex or levator scapulae muscle, which act to compensate for the lack of shoulder movement in patients with frozen shoulder. These two muscles showed thickening and hypoechoic changes upon sonography. Full article
(This article belongs to the Special Issue Bone Regeneration, Osteoclastogenesis, Osteoporosis and Osteoarthritis)
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21 pages, 18578 KiB  
Article
ABCG2 Gene Expression in Non-Small Cell Lung Cancer
by Agnieszka Jeleń, Marta Żebrowska-Nawrocka, Mariusz Łochowski, Dagmara Szmajda-Krygier and Ewa Balcerczak
Biomedicines 2024, 12(10), 2394; https://doi.org/10.3390/biomedicines12102394 - 19 Oct 2024
Viewed by 1334
Abstract
Background/Objectives: ATP-binding cassette subfamily G member 2 [ABCG2/breast cancer resistance protein (BCRP)] contributes to mechanisms of multidrug resistance (MDR) and is a marker of side population (SP) cells in human cancers. The primary objective of this study was to investigate the impact of [...] Read more.
Background/Objectives: ATP-binding cassette subfamily G member 2 [ABCG2/breast cancer resistance protein (BCRP)] contributes to mechanisms of multidrug resistance (MDR) and is a marker of side population (SP) cells in human cancers. The primary objective of this study was to investigate the impact of ABCG2 gene expression on the non-small cell lung cancer (NSCLC) development, course of cancer disease, and patient prognosis using publicly available data. Obtained results were supplemented with assessment of ABCG2 expression in blood of NSCLC patients. Methods: The dataset of lung cancer was analyzed utilizing the TIMER 2.0, UALCAN, TNMplot, MEXPRESS, cBioPortal, MethSurv, KM Plotter, STRING, and ShinyGO 0.80 databases. Blood samples from 50 patients were assessed using the real-time PCR method. Results: The ABCG2 gene was expressed at a low level in NSCLC, and did not correlate with clinical aggressiveness of lung cancer. Higher ABCG2 expression improved overall survival, but only in LUAD. In addition, CpG sites located on the CpG island affecting the NSCLC patient’s prognosis were indicated. In the case of our own laboratory results, the study did not reveal any changes in the ABCG2 expression levels in blood collected from patients at different time points during the diagnostic–therapeutic procedure. In the in silico analysis, most ABCG2 protein interactors were associated with the development of drug resistance. Conclusions: ABCG2 appears to have a particularly significant impact on the survival of patients with lung cancer and on the effect of immunotherapy related to immune cell infiltration. Presented findings may support personalized medicine strategies based on bioinformatics findings. Full article
(This article belongs to the Special Issue Molecular Biomarkers of Tumors: Advancing Genetic Studies)
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14 pages, 2504 KiB  
Article
Circulating Serum Micro-RNA as Non-Invasive Diagnostic Biomarkers of Endometriosis
by Antonella Ravaggi, Cosetta Bergamaschi, Chiara Galbiati, Laura Zanotti, Aline S. C. Fabricio, Massimo Gion, Elia Cappelletto, Antonette E. Leon, Massimo Gennarelli, Cesare Romagnolo, Giuseppe Ciravolo, Stefano Calza, Eliana Bignotti and Franco Odicino
Biomedicines 2024, 12(10), 2393; https://doi.org/10.3390/biomedicines12102393 - 19 Oct 2024
Viewed by 751
Abstract
Background/Objectives: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful [...] Read more.
Background/Objectives: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful non-invasive biomarkers for END. The aim of this study was to perform serum miRNA profiling in a retrospective cohort of women to identify miRNAs that are differentially expressed in END compared to control patients. Methods: RNA was isolated from serum samples of 67 END patients and 60 control women. The expression profile of a 754-miRNA panel was studied with RT-qPCR performed on a QuantStudio 12K Flex with the TaqMan OpenArray miRNA panel. A Censored Regression Model was used for miRNA differential expression analysis. Several gene-enrichment algorithms were employed to identify pathways related to the target genes of differentially expressed miRNAs. Results: One hundred and thirty miRNAs were detected in at least 75% of samples from either the END or the control group. Sixteen miRNAs were significantly modulated between the END and control groups. Enrichment analysis identified targets significantly overrepresented in numerous pathways involved in biological processes related to END, including inflammation, angiogenesis, cellular invasion, cell-cycle/cell proliferation, and estrogen and progesterone hormonal signaling. Conclusions: Our study indicates that differentially expressed miRNAs between END patients and controls can be identified through liquid biopsy. Our findings also suggest a potential role for serum miRNAs in the pathophysiology of END, warranting further investigations for their use as non-invasive biomarkers. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 4.0)
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13 pages, 2388 KiB  
Article
Effects of Far-Infrared Rays Emitted from Loess Bio-Balls on Lymphatic Circulation and Reduction of Inflammatory Fluids
by Yong Il Shin, Min Seok Kim, Yeong Ae Yang, Gye Rok Jeon, Jae Ho Kim, Yeon Jin Choi, Woo Cheol Choi and Jae Hyung Kim
Biomedicines 2024, 12(10), 2392; https://doi.org/10.3390/biomedicines12102392 - 19 Oct 2024
Viewed by 529
Abstract
Background: FIR therapy is used in various medical settings to treat diseases associated with inflammation and edema. Unlike conventional FIR lamp therapy, this study investigated how body fluids change depending on the intensity and duration of FIR irradiation to the whole body. [...] Read more.
Background: FIR therapy is used in various medical settings to treat diseases associated with inflammation and edema. Unlike conventional FIR lamp therapy, this study investigated how body fluids change depending on the intensity and duration of FIR irradiation to the whole body. Method: Subjects in group A (n = 27) were exposed to FIR emitted from a loess bio-ball mat set at 40 °C for 30 min, and subjects in group B (n = 27) were exposed to FIR emitted from a loess bio-ball mat set at 30 °C for 7 h during sleep. Changes in bioimpedance parameters and fluid-related values were measured using a body fluid analyzer before and after exposure to FIR. Results: Changes in bioimpedance parameters associated with inflammatory fluids were quantitatively confirmed. In group A, there was a minimal change in fluid-related measurements. However, significant changes in bioimpedance parameters associated with inflammatory fluids were observed in group B exposure to FIR for 7 h during sleep. Conclusions: FIR emitted from loess bio-balls activates biological tissues and lymphatic circulation, gradually reducing the levels of inflammatory fluids over time. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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12 pages, 1222 KiB  
Article
Hyperosmotic Stress Induces the Expression of Organic Osmolyte Transporters in Porcine Intestinal Cells and Betaine Exerts a Protective Effect on the Barrier Function
by Elena De Angelis, Paolo Borghetti, Benedetta Passeri, Valeria Cavalli, Luca Ferrari, Melania Andrani, Paolo Martelli and Roberta Saleri
Biomedicines 2024, 12(10), 2391; https://doi.org/10.3390/biomedicines12102391 - 18 Oct 2024
Viewed by 603
Abstract
Background/objectives: The porcine intestinal epithelium plays a fundamental role as a defence interface against pathogens. Its alteration can cause severe inflammatory conditions and diseases. Hyperosmotic stress under physiological conditions and upon pathogen challenge can cause malabsorption. Different cell types counteract the osmolarity increase [...] Read more.
Background/objectives: The porcine intestinal epithelium plays a fundamental role as a defence interface against pathogens. Its alteration can cause severe inflammatory conditions and diseases. Hyperosmotic stress under physiological conditions and upon pathogen challenge can cause malabsorption. Different cell types counteract the osmolarity increase by accumulating organic osmolytes such as betaine, taurine, and myo-inositol through specific transporters. Betaine is known for protecting cells from hyperosmotic stress and has positive effects when fed to pigs. The aim of this study is to demonstrate the modulation of osmolyte transporters gene expression in IPEC-J2 during osmolarity changes and assess the effects of betaine. Methods: IPEC-J2 were seeded in transwells, where differentiate as a polarized monolayer. Epithelial cell integrity (TEER), oxidative stress (NO) and gene expression of osmolyte transporters, tight junction proteins (TJp) and pro-inflammatory cytokines were evaluated. Results: Cells treated with NaCl hyperosmolar medium (500 mOsm/L) showed a TEER decrease at 3 h and detachment within 24 h, associated with an osmolyte transporters reduction. IPEC-J2 treated with mannitol hyperosmolar medium (500 mOsm/L) upregulated taurine (TauT), myo-inositol (SMIT) and betaine (BGT1) transporters expression. A decrease in TJp expression was associated with a TEER decrease and an increase in TNFα, IL6, and IL8. Betaine could attenuate the hyperosmolarity-induced reduction in TEER and TJp expression, the NO increase and cytokines upregulation. Conclusions: This study demonstrates the expression of osmolyte transporters in IPEC-J2, which was upregulated upon hyperosmotic treatment. Betaine counteracts changes in intracellular osmolarity by contributing to maintaining the epithelial barrier function and reducing the inflammatory condition. Compatible osmolytes may provide beneficial effects in therapies for diseases characterized by inflammation and TJp-related dysfunctions. Full article
(This article belongs to the Special Issue The Role of Intestinal Epithelial Cells and Their Cellular Interactions)
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25 pages, 2942 KiB  
Review
ABCA3 c.838C>T (p.Arg280Cys, R280C) and c.697C>T (p.Gln233Ter, Q233X, Q233*) as Causative Variants for RDS: A Family Case Study and Literature Review
by Maria Livia Ognean, Mădălina Anciuc-Crauciuc, Radu Galiș, Alex-Emilian Stepan, Mioara Desdemona Stepan, Claudia Bănescu, Florin Grosu, Boris W. Kramer and Manuela Cucerea
Biomedicines 2024, 12(10), 2390; https://doi.org/10.3390/biomedicines12102390 - 18 Oct 2024
Viewed by 693
Abstract
Background: Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5–7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal [...] Read more.
Background: Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5–7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature are inconsistent. Material and Methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, which was not previously reported but is a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, an analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis. Full article
(This article belongs to the Special Issue Biomedical Advances in ABC Transporters: From Bench to Bedside)
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28 pages, 825 KiB  
Review
From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches
by Qingmei Li, Jihan Wang and Congzhe Zhao
Biomedicines 2024, 12(10), 2389; https://doi.org/10.3390/biomedicines12102389 - 18 Oct 2024
Viewed by 787
Abstract
Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies—genomics, transcriptomics, proteomics, and metabolomics—have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic [...] Read more.
Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies—genomics, transcriptomics, proteomics, and metabolomics—have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions. Full article
(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)
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17 pages, 1085 KiB  
Article
Enhancing Brain Tumor Diagnosis with L-Net: A Novel Deep Learning Approach for MRI Image Segmentation and Classification
by Lehel Dénes-Fazakas, Levente Kovács, György Eigner and László Szilágyi
Biomedicines 2024, 12(10), 2388; https://doi.org/10.3390/biomedicines12102388 - 18 Oct 2024
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Abstract
Background: Brain tumors are highly complex, making their detection and classification a significant challenge in modern medical diagnostics. The accurate segmentation and classification of brain tumors from MRI images are crucial for effective treatment planning. This study aims to develop an advanced neural [...] Read more.
Background: Brain tumors are highly complex, making their detection and classification a significant challenge in modern medical diagnostics. The accurate segmentation and classification of brain tumors from MRI images are crucial for effective treatment planning. This study aims to develop an advanced neural network architecture that addresses these challenges. Methods: We propose L-net, a novel architecture combining U-net for tumor boundary segmentation and a convolutional neural network (CNN) for tumor classification. These two units are coupled such a way that the CNN classifies the MRI images based on the features extracted by the U-net while segmenting the tumor, instead of relying on the original input images. The model is trained on a dataset of 3064 high-resolution MRI images, encompassing gliomas, meningiomas, and pituitary tumors, ensuring robust performance across different tumor types. Results: L-net achieved a classification accuracy of up to 99.6%, surpassing existing models in both segmentation and classification tasks. The model demonstrated effectiveness even with lower image resolutions, making it suitable for diverse clinical settings. Conclusions: The proposed L-net model provides an accurate and unified approach to brain tumor segmentation and classification. Its enhanced performance contributes to more reliable and precise diagnosis, supporting early detection and treatment in clinical applications. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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Review
Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart–Brain Axis
by Teresa Soda, Teresa Pasqua, Giovambattista De Sarro and Francesco Moccia
Biomedicines 2024, 12(10), 2387; https://doi.org/10.3390/biomedicines12102387 - 18 Oct 2024
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Abstract
Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong [...] Read more.
Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart–brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments. Full article
(This article belongs to the Section Cell Biology and Pathology)
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