Biomedicines

10 pages, 2874 KiB

Open AccessArticle

A Statistical Approach to Assess Biological Equivalent Mean Organ Dose (MOD) for Different Fractionations in Thoracic Radiotherapy

by Siyao Zhong, Guangshan Wang, Xiaohang Qin, Yinghui Li, Bin Sun, Feng-Ming (Spring) Kong, Yuyan Gao and Jian-Yue Jin

Biomedicines 2025, 13(5), 1110; https://doi.org/10.3390/biomedicines13051110 - 2 May 2025

Abstract

Background: With advances in radiotherapy technology, there are more technological options and fractionation regiments for different stages of lung cancer. Evaluation of the possibility of severe organ toxicity for the organ-at-risks (OARs) is often required when treating patients with unusual fractionations or combining [...] Read more.

Background: With advances in radiotherapy technology, there are more technological options and fractionation regiments for different stages of lung cancer. Evaluation of the possibility of severe organ toxicity for the organ-at-risks (OARs) is often required when treating patients with unusual fractionations or combining two treatment plans with different fractionations. Purpose: This study aims to provide an approach that can reasonably estimate the possibility of toxicity using a biological equivalent mean organ dose (MOD)-based model from the 2 Gy per fraction era for various fractionations. Methods and Materials: The dose volume histograms (DVHs) of 272 patients treated with radiotherapy for lung cancer at a prescribed dose of 2 Gy × 30 f were used for analysis. For each patient, we calculated the biological equivalent MOD based on a dose conversion of EQD2 (equivalent to a dose of 2 Gy/fraction to the organ), the MOD based on the physical dose, and the d-value that makes the biological equivalent MOD based on a dose conversion of EQDd equal to the physical MOD. Statistical analysis was then performed to determine the relationship of the d-value to the corresponding physical MOD in percentage dose (relative MOD). Results: Equivalent MODs based on EQD2 were smaller than the physical MOD for each patient, suggesting that using EQD2 conversion would underestimate the equivalent MOD. The distribution of d-values with physical relative mean lung dose (RMLD) showed a normal peak with an average of d = 1.3 Gy, suggesting that the equivalent MLD can be estimated using EQD1.3 for various fractionations. Regression analysis showed that the d-value could be estimated as d =

\sqrt{0.93 + 3.0 \times R M L D}

, d =

\sqrt{0.044 + 5.8 \times R M E D}

, and d =

\sqrt{4.7 \times R M H D}

for the lung, esophagus, and heart, respectively, suggesting that the equivalent MLD, MED, and MHD can be estimated using EQDd. Conclusions: Using EQD2 conversion underestimates the equivalent MOD, and the equivalent MOD converted by EQDd with an appropriate d-value may enhance the assessment of organ toxicity. Full article

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

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10 pages, 250 KiB

Open AccessReview

Navigating Sarcopenia Risks in GLP-1RA Therapy for Advanced Heart Failure

by Winston Wang, Danielle Green, Ramzi Ibrahim, Mahmoud Abdelnabi, Hoang Nhat Pham, Beani Forst, Mohamed Allam, Patrick Sarkis, George Bcharah, Juan Farina, Chadi Ayoub, Dan Sorajja and Reza Arsanjani

Biomedicines 2025, 13(5), 1108; https://doi.org/10.3390/biomedicines13051108 - 2 May 2025

Abstract

Cardiac cachexia (CC) is a severe complication of advanced heart failure (HF), characterized by involuntary weight loss and muscle wasting, leading to poor outcomes and higher mortality. Despite its severity, CC remains under-recognized and undertreated, lacking targeted therapies specifically addressing its pathophysiology. Glucagon-like [...] Read more.

Cardiac cachexia (CC) is a severe complication of advanced heart failure (HF), characterized by involuntary weight loss and muscle wasting, leading to poor outcomes and higher mortality. Despite its severity, CC remains under-recognized and undertreated, lacking targeted therapies specifically addressing its pathophysiology. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), though beneficial in reducing cardiovascular risk in patients with HF, may exacerbate muscle wasting in cachectic patients, necessitating further investigation. Non-pharmacological strategies, including tailored nutritional support and exercise programs, have shown positive effects on body composition and quality of life in patients with CC. However, there remains a gap in recommendations tailored to preventive strategies and pharmacologic therapies for patients with CC and concomitant GLP-1RA use. This review highlights the multifactorial mechanisms underlying CC and current and emerging therapeutic approaches for mitigating HF-related sarcopenia while on GLP-1RAs. Full article

(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—4th Edition)

10 pages, 458 KiB

Open AccessArticle

Risk Factors for the Development of Early Onset Diabetes in the Population of Sindh Province, Pakistan

by Eraj Abbas, Asher Fawwad, Iftikhar Ahmed Siddiqui, Muhammad Sohail Afzal, Muhammad Ansar, Muhammad Arif Nadeem Saqib and Syed M. Shahid

Biomedicines 2025, 13(5), 1107; https://doi.org/10.3390/biomedicines13051107 - 2 May 2025

Abstract

Background/Objective: Early-onset diabetes (EOD), diagnosed at ≤35 years, is a growing public health crisis in low- and middle-income countries, including Pakistan. Identifying modifiable and non-modifiable risk factors is critical for developing effective prevention strategies. This study aimed to investigate the risk factors [...] Read more.

Background/Objective: Early-onset diabetes (EOD), diagnosed at ≤35 years, is a growing public health crisis in low- and middle-income countries, including Pakistan. Identifying modifiable and non-modifiable risk factors is critical for developing effective prevention strategies. This study aimed to investigate the risk factors associated with EOD in Sindh, Pakistan, focusing on genetic, lifestyle, and metabolic determinants. Methods: A multicenter cross-sectional study was conducted across diabetic clinics in Sindh, with primary data collection at Baqai Institute of Diabetology and Endocrinology (Karachi, Pakistan) and secondary sites in Hyderabad, Larkana, and Sukkur. Following institutional ethical approval and informed consent, we enrolled 754 individuals (type 1 and type 2 diabetes, age at diagnosis: 15–35 years). Data on anthropometric, clinical, biochemical, and lifestyle parameters were collected via structured questionnaires. Statistical analyses included Pearson’s Chi Square tests and multivariate logistic regression in determining associations. Results: Logistic regression revealed key predictors of early-onset diabetes (EOD). A two-generation diabetes family history showed a strong association (aOR:1.86, 1.12–3.43). Significant lifestyle risks included physical inactivity (OR:1.40, 1.03–1.90), frequent sugary beverage intake (OR:1.93, 1.89–1.98), and abnormal sleep duration (<6 h: OR:1.58, 1.04–2.40; >8 h: OR:1.86, 1.21–2.85). Hypertension was a major metabolic predictor (elevated BP: OR:1.79, 1.28–1.54; Stage I: OR:1.81, 1.34–1.77). Cardiovascular disease and uncontrolled fasting glucose lost significance after adjustment, indicating confounding effects. Conclusions: This study highlights familial predisposition, sedentary behavior, poor diet, sleep disturbances, and hypertension as key contributors to EOD in young Pakistani adults. Early screening and targeted lifestyle interventions are urgently needed to mitigate this escalating epidemic. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (2nd Edition))

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21 pages, 2536 KiB

Open AccessArticle

Quantification of the Dynamics of the Vascular Flows in the Cerebral Arterial and Venous Trees

by Heimiri Monnier, Kimi Owashi, Pan Liu, Serge Metanbou, Cyrille Capel and Olivier Balédent

Biomedicines 2025, 13(5), 1106; https://doi.org/10.3390/biomedicines13051106 - 1 May 2025

Abstract

Objective: Cerebral vascularization is made of the symmetrical arterial system, with muscular walls, and the venous system, more variable and dominated by sinuses and jugular veins. Factors like age and posture influence this network, complicating its study. Phase-contrast MRI is the gold standard [...] Read more.

Objective: Cerebral vascularization is made of the symmetrical arterial system, with muscular walls, and the venous system, more variable and dominated by sinuses and jugular veins. Factors like age and posture influence this network, complicating its study. Phase-contrast MRI is the gold standard for quantifying cerebral circulation. This study aimed to quantify the dynamics of the cerebral blood system using PC-MRI. Materials and Methods: Thirty-six healthy adults participated. Imaging was performed on a 3T MRI (Philips Achieva) in a supine position. Two slices were acquired: intracranial and extracranial. In-house software analyzed flow curves over a cardiac cycle. Each vessel’s contribution was evaluated. Results: Extracranial venous drainage was categorized as jugular-dominant, equivalent, or peripheral-dominant. A similar classification applied intracranially. Intracranial flows showed low variability (5–9%), while extracranial venous flows, especially in the internal jugular veins, had higher variability (17–21%). Some extracranial veins were absent. Conclusions: There is significant venous heterogeneity in the extracranial region. PC-MRI enables the quantification of cerebral dynamics. Full article

(This article belongs to the Section Molecular and Translational Medicine)

10 pages, 997 KiB

Open AccessCommunication

Stability of BTI Devices for Plasma Rich in Growth Factors (PRGF) Eye Drop Delivery Under Varying Storage and Handling Conditions

by Eduardo Anitua, Iraia Reparaz, María de la Fuente and Mohammad Hamdan Alkhraisat

Biomedicines 2025, 13(5), 1105; https://doi.org/10.3390/biomedicines13051105 - 1 May 2025

Abstract

Purpose: To evaluate the sterility and biological functionality of platelet lysate eye drops stored in BTI ophthalmic devices for PRGF delivery under different storage conditions and simulated use scenarios. Methods: Eye drops were prepared using platelet lysate and stored in BTI [...] Read more.

Purpose: To evaluate the sterility and biological functionality of platelet lysate eye drops stored in BTI ophthalmic devices for PRGF delivery under different storage conditions and simulated use scenarios. Methods: Eye drops were prepared using platelet lysate and stored in BTI tubes under three different conditions: ≤−15 °C, 2–8 °C, and room temperature (RT) for 72 h. Simulated use was performed for 72 h with controlled drop dispensing. Bacterial contamination was assessed according to European Pharmacopoeia sterility testing principles. The biological activity of the eye drops was assessed using in vitro proliferation assays with primary human keratocytes (HKs) and human corneal epithelial cells (HCEs). Statistical analyses were performed to compare the effects of different storage conditions and application scenarios. Results: No bacterial contamination was detected in platelet lysate eye drops stored under any of the conditions tested, regardless of simulated use. Proliferation assays showed that eye drops enhanced the growth of HK and HCE cells compared to the control medium. No significant differences in proliferation were observed between storage conditions. Conclusions: Platelet lysate eye drops maintain sterility and biological functionality when stored in BTI ophthalmic devices at ≤−15 °C, 2–8 °C and RT for up to 72 h of simulated use. These results support the feasibility of using BTI eye drop devices in clinical settings while ensuring safety and efficacy. Full article

(This article belongs to the Section Biomedical Engineering and Materials)

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15 pages, 914 KiB

Open AccessArticle

A Comprehensive Comparison of PICSI and ICSI Techniques Through a Triple-Blinded Trial: Effects on Embryo Quality, Cumulative Pregnancy Rate, and Live Birth Rate

by Lucia Alegre, Laura Carrión-Sisternas, Lorena Bori, Irene Hervás, Jose Remohí, Nicolás Garrido and Marcos Meseguer

Biomedicines 2025, 13(5), 1104; https://doi.org/10.3390/biomedicines13051104 - 1 May 2025

Abstract

Background: Sperm selection is critical in assisted reproduction, typically relying on swim-up and centrifugation density gradients. New methods, such as PICSI (physiological intracytoplasmic sperm selection), aim to enhance outcomes by selecting mature sperm based on hyaluronic acid (HA) binding and have generated [...] Read more.

Background: Sperm selection is critical in assisted reproduction, typically relying on swim-up and centrifugation density gradients. New methods, such as PICSI (physiological intracytoplasmic sperm selection), aim to enhance outcomes by selecting mature sperm based on hyaluronic acid (HA) binding and have generated interest due to their potential impact on the clinical outcomes of patients who undergo assisted reproductive treatments. Methods: A single-center, prospective, and triple-blinded study was conducted with 277 couples in the egg donation program. The oocytes of each recipient patient were randomly microinjected using the ICSI or PICSI technique and maintained in culture in time-lapse incubators until blastocyst formation. Biological and clinical outcomes were analyzed, including fertilization and blastocyst formation rates, embryo morphokinetics, pregnancy, miscarriage, and live birth rates, and artificial intelligence-assigned embryo quality scores. Results: Clinical outcomes were comparable between the two groups, but a higher pregnancy rate was observed in the PICSI group than in the ICSI group (74.04% vs. 70.87%). Although blastocyst formation rates were similar on both day 5 (D5) and day 6 of development, the proportion of good-quality embryos on D5 was higher in the PICSI group (68.27%) than in the ICSI group (63.47%) (p > 0.05). Finally, the cumulative pregnancy rate was significantly higher in the experimental group than in the control group (88% vs. 72%) after four embryo transfers (p < 0.05). Conclusions: Utilizing HA to perform sperm selection during ICSI procedures does not increase live birth rates. However, it may enhance the quality of the selected sperm. This could be beneficial for patients in egg donation programs, particularly for those who have experienced repeated pregnancy loss. Full article

(This article belongs to the Special Issue Molecular Regulation of Spermatozoa—Second Edition)

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22 pages, 1325 KiB

Open AccessReview

The Power of Movement: How Exercise Influences Chemotherapy-Induced Peripheral Neuropathy

by Joana Loureiro, José Tiago Costa-Pereira, Daniel H. Pozza and Isaura Tavares

Biomedicines 2025, 13(5), 1103; https://doi.org/10.3390/biomedicines13051103 - 1 May 2025

Abstract

As the number of cancer patients and survivors increases, we face a rising challenge: the long-term impact of the adverse effects of cancer treatment. One of the known adverse effects is chemotherapy-induced peripheral neuropathy (CIPN), which courses with pain complaints. The treatments of [...] Read more.

As the number of cancer patients and survivors increases, we face a rising challenge: the long-term impact of the adverse effects of cancer treatment. One of the known adverse effects is chemotherapy-induced peripheral neuropathy (CIPN), which courses with pain complaints. The treatments of CIPN have reduced efficacy. The neurobiological causes of CIPN have been mainly ascribed to peripheral nerve damage, but recent studies show effects in the brain, namely in the descending pain modulatory systems. Physical exercise seems to be associated with better outcomes in CIPN patients, but the mechanisms underlying the effects have not been discussed, namely considering the recent results of the effects of CIPN in brain structures involved in pain modulation. In this critical review, we propose that the beneficial effects of exercise in CIPN also have central mechanisms, namely neuroinflammation and oxidative stress, as well as changes in the actions of neurotransmitters and neurotrophic factors, with a direct effect on optimizing the endogenous pain modulation, namely opioids, monoamines, and endocannabinoids. The effects are multifactorial, as mood improvement and the other psychological benefits of exercise should be considered. The emerging role of the microbiome, which is affected during CIPN, also needs to be considered. This review critically synthesizes the available literature to highlight how the neurobiological effects of physical exercise make it a promising strategy for managing CIPN, both from preventive and treatment perspectives. Full article

(This article belongs to the Special Issue Chronic Pain: From Prevention to Therapeutic Strategies—Second Edition)

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15 pages, 1752 KiB

Open AccessArticle

Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation

by Małgorzata Sobańska, Dawid Sobański, Rafał Staszkiewicz, Paweł Gogol, Damian Strojny, Tomasz Pawłaszek, Werner Dammerman and Beniamin Oskar Grabarek

Biomedicines 2025, 13(5), 1102; https://doi.org/10.3390/biomedicines13051102 - 1 May 2025

Abstract

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial [...] Read more.

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. Methods: We analyzed NRTN mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. Results: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (p < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA p = 0.032 for mRNA, p = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, p = 0.015) and diabetes (β = 0.39, p = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (p = 0.046), while smoking showed no significant independent effect. Conclusions: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation. Full article

(This article belongs to the Special Issue Pathogenesis and Novel Therapeutics in Musculoskeletal Conditions, 3rd Edition)

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10 pages, 920 KiB

Open AccessArticle

Add-On Treatment with Gliclazide for Cancer Patients with Type 2 Diabetes Undergoing Cyclic Glucocorticoid-Containing Chemotherapy

by Seung Eun Lee, Ju-Hyun Park, Dalyong Kim, Hyun-A Lee, Yun Seong Kang, Young Soon Yoon, Yun Jeong Jeong, Han Seok Choi and Kyoung-Ah Kim

Biomedicines 2025, 13(5), 1101; https://doi.org/10.3390/biomedicines13051101 - 1 May 2025

Abstract

Aims: Despite its high prevalence, studies on glucocorticoid-induced hyperglycemia are lacking. We examined the glucose profiles of patients with type 2 diabetes undergoing dexamethasone-containing chemotherapy using continuous glucose monitoring (CGM). We also investigated the effects of gliclazide on the management of hyperglycemia [...] Read more.

Aims: Despite its high prevalence, studies on glucocorticoid-induced hyperglycemia are lacking. We examined the glucose profiles of patients with type 2 diabetes undergoing dexamethasone-containing chemotherapy using continuous glucose monitoring (CGM). We also investigated the effects of gliclazide on the management of hyperglycemia in these patients. Materials and Methods: Seventeen patients with type 2 diabetes who received cyclic chemotherapy with dexamethasone were enrolled in this study. During the first cycle, iPro2, a blinded CGM device, was applied for 7 days. If a patient’s CGM data exhibited an increase of 20% or more in the mean glucose level after dexamethasone administration, they received the second cycle, unless they had already received sulfonylurea or their chemotherapy regimen had changed. During the second cycle, the patients were treated with gliclazide as an add-on to their routine diabetic medication. Results: Dexamethasone treatment significantly increased glucose levels, especially in patients with a longer diabetes duration (8.4 years vs. 1.2 years, p = 0.009). For the nine patients who proceeded to the second cycle, gliclazide treatment significantly ameliorated hyperglycemia. Time in range increased from 33.11% to 45.22% (p = 0.020), and time above range significantly decreased from 66.89% to 52.78% (p = 0.003). The glucose management indicators were 9.52% and 8.40% for pre- and post-gliclazide treatment, respectively. One patient visited the emergency department because of symptomatic hypoglycemia. Conclusions: Chemotherapy regimens containing dexamethasone result in high blood glucose levels even after the last dexamethasone dose in patients with pre-existing diabetes. Adding gliclazide could be beneficial in managing hyperglycemia during dexamethasone-containing chemotherapy. Full article

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

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10 pages, 953 KiB

Open AccessArticle

Clinical Significance of Tumor Grade in Triple-Negative Breast Cancer: A Retrospective Cohort Analysis

by Neya Ramanan, Mah-noor Malik, Sarang Upneja, Haniya Farooq, Swati Kulkarni, Rasna Gupta, John Mathews, Abdullah Nasser, Alina Bocicariu, Laurice Arayan, Lisa Porter, Bre-Anne Fifield, Rong Luo, Muriel Brackstone and Caroline Hamm

Biomedicines 2025, 13(5), 1100; https://doi.org/10.3390/biomedicines13051100 - 1 May 2025

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) proteins. Here, we investigated the prognostic value of grade in patients with TNBC. Methods: This retrospective study analyzed 780 [...] Read more.

Triple-negative breast cancer (TNBC) is a heterogeneous cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) proteins. Here, we investigated the prognostic value of grade in patients with TNBC. Methods: This retrospective study analyzed 780 TNBC patients from two large regional cancer programs in Canada. Patients seen between 1 January 2004 and 31 December 2022 were included. Patients with grade 1 tumors and stage IV disease were excluded from analysis. Demographic information regarding the patient, tumor, and treatment were collected. The primary outcomes, relapse-free survival (RFS) and overall survival (OS), were analyzed using the Cox proportional hazards model and max-combo test. Results: For patients with grade 2 TNBC, median RFS was 14.1 years (95% CI, 9.48 to not reached (NR)) while it was not reached for patients with grade 3 tumors. No difference for relapse was identified in the first five years. Beyond 5 years, 4.9% of the patients with grade 2 tumors and 1.6% of those with grade 3 tumors relapsed (p = 0.006). In that same study period, 10.4% of patients with grade 2 tumors and 5.7% of those with grade 3 tumors died (p = 0.03). Conclusion: Grade 2 TNBC was associated with a higher risk of relapse and death after the 5-year mark compared to grade 3 TNBC. This distinct pattern of relapse and survival in grade 2 TNBC, characterized by an increased risk of relapse and mortality after 5 years, warrants confirmatory investigations. Full article

(This article belongs to the Special Issue Triple Negative Breast Cancer: From Mechanisms to Therapeutic Approaches)

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18 pages, 605 KiB

Open AccessReview

Tumor-Associated Macrophages as Key Modulators of Disease Progression in Diffuse Large B-Cell Lymphoma

by Corina Joldes, Laura Jimbu, Oana Mesaros, Mihnea Zdrenghea and Bogdan Fetica

Biomedicines 2025, 13(5), 1099; https://doi.org/10.3390/biomedicines13051099 - 1 May 2025

Abstract

With the advent of new therapeutic approaches, there is hope that anticancer treatment will eventually be possible without the use of chemotherapy. Efficient immunotherapeutic options have recently emerged in many cancers, offering a less aggressive approach, with overall better tolerance, making them also [...] Read more.

With the advent of new therapeutic approaches, there is hope that anticancer treatment will eventually be possible without the use of chemotherapy. Efficient immunotherapeutic options have recently emerged in many cancers, offering a less aggressive approach, with overall better tolerance, making them also suitable for frail patients. Response to immunotherapy relies on the availability, functionality, and efficacy of the host’s immune effector mechanisms. One of the key factors determining the efficacy of immunotherapy is the tumor microenvironment, which encompasses various immune effectors, including macrophages, which play a crucial role in regulating immune responses through phagocytosis and antigen presentation. Macrophages are prototypically divided, according to their polarization, into either the pro-inflammatory M1 type or the anti-inflammatory M2 type. In the tumor microenvironment, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), are the predominant phenotype and are associated with tumor progression. The M1/M2 paradigm contributes to the understanding of tumor progression. Due to the variable microenvironment, the mechanisms regulating TAMs can vary across different cancers. Variations in TAM polarization may account for the different treatment responses in patients with similar diseases. This paper investigates the connection between TAMs, disease progression, and treatment responses in the most frequent solid hematologic cancer, diffuse large B-cell lymphoma. Full article

(This article belongs to the Collection Advances in Leukocyte Biology)

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20 pages, 1087 KiB

Open AccessReview

Adipokines and Adipose Tissue: The Role and Use of Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors in Patients with Diabetes or Heart Failure

by Michalina Mazurkiewicz, Patryk Bodnar, Dominika Blachut, Tomasz Chwalba, Wiktor Wagner, Eliza Barczyk, Ewa Romuk, Wojciech Jacheć and Celina Wojciechowska

Biomedicines 2025, 13(5), 1098; https://doi.org/10.3390/biomedicines13051098 - 30 Apr 2025

Abstract

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have become integral in treating both diabetes mellitus and heart failure, independent of left ventricular ejection fraction. Their pleiotropic effect influences multiple mechanisms, enhancing the function of various systems within the body. They exhibit nephroprotective and cardioprotective effects [...] Read more.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have become integral in treating both diabetes mellitus and heart failure, independent of left ventricular ejection fraction. Their pleiotropic effect influences multiple mechanisms, enhancing the function of various systems within the body. They exhibit nephroprotective and cardioprotective effects by improving cell metabolism, endothelial function, and slowing the fibrosis of the cardiac muscle, and they also have a beneficial impact on other organs. At the cellular level, they protect against the harmful effects of free radicals both by lowering glucose levels and by supporting the function of the antioxidant system. Moreover, SGLT-2 inhibitors can modify the metabolism of adipocytes by affecting the production of cytokines such as adiponectin—which increases insulin sensitivity, leading to weight loss and improved glycemic control. Full article

(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)

11 pages, 240 KiB

Open AccessArticle

Cardio-Respiratory Fitness and Fatigue in Post-COVID-19 Syndrome—A Three-Year Update

by Radostina Cherneva, Zheyna Cherneva, Vania Youroukova, Tanya Kadiyska, Dinko Valev, Ebru Myuyun Hayrula-Manaf and Vanyo Mitev

Biomedicines 2025, 13(5), 1097; https://doi.org/10.3390/biomedicines13051097 - 30 Apr 2025

Abstract

Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of [...] Read more.

Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of physical activity, according to the fatigue severity score, and analyze its association with basic cardio-pulmonary exercise testing (CPET) parameters. Methods: A total of 192 subjects with history of SARSCoV-2 infection were included. They filled in the Chronic Fatigue Syndrome Questionnaire (CFSQ) and were divided into symptomatic and asymptomatic groups. Forty-seven had persistent post-COVID complaints—reduced physical capacity, fatigue, dyspnea, sleep disturbances, muscle pain. CPET was performed and the pathophysiological parameters in the different fatigue severity groups were compared. Results: Subjects with persistent long-term PCS were divided into two groups—mild (20) and moderate–severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. The average period between the acute illness and the study was 1028 ± 214 days. Subjects with moderate–severe PCS had more symptoms during CPET (73.6% vs. 24.8% vs. 17.4%), as compared to mild/asymptomatic. The rate of perceived effort was subjective and did not correspond to the workload, heart, or breathing rate in the symptomatic group. These subjects were unable to reach the anaerobic threshold, compared to mild/asymptomatic subjects (51.8% vs. 25%, vs. 12.5%). Patients with moderate–severe PCS showed lower peak VO₂ (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to mild/asymptomatic subjects. Conclusions: Long-term PCS is still present in up to 24% of the general population, more than thirty months after the acute episode. It is characterized by increased perception of symptom burden and diminished aerobic metabolism. A third of the long-term PCS exhibit lower cardio-respiratory fitness, independently from the severity of the symptoms. Full article

(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition)

2 pages, 3002 KiB

Open AccessCorrection

Correction: Xie et al. Exploring the Mechanisms and Preventive Strategies for the Progression from Idiopathic Pulmonary Fibrosis to Lung Cancer: Insights from Transcriptomics and Genetic Factors. Biomedicines 2024, 12, 2382

by Kai Xie, Xiaoyan Tan, Zhe Chen, Yu Yao, Jing Luo, Haitao Ma, Yu Feng and Wei Jiang

Biomedicines 2025, 13(5), 1096; https://doi.org/10.3390/biomedicines13051096 - 30 Apr 2025

Abstract

In the original publication, there was a mistake in Figure 11 as published [...] Full article

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

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16 pages, 2440 KiB

Open AccessSystematic Review

Evaluating the Causal Association Between Type 2 Diabetes and Alzheimer’s Disease: A Two-Sample Mendelian Randomization Study

by Si Han, Tom Lelieveldt, Miriam Sturkenboom, Geert Jan Biessels and Fariba Ahmadizar

Biomedicines 2025, 13(5), 1095; https://doi.org/10.3390/biomedicines13051095 - 30 Apr 2025

Abstract

Background/Objectives: Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are significant global health issues. Epidemiological studies suggest T2DM increases AD risk, though confounding factors and reverse causality complicate this association. This study aims to clarify the causal relationship between T2DM and [...] Read more.

Background/Objectives: Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are significant global health issues. Epidemiological studies suggest T2DM increases AD risk, though confounding factors and reverse causality complicate this association. This study aims to clarify the causal relationship between T2DM and AD through a systematic review and meta-analysis of Mendelian randomization (MR) studies and a new two-sample MR analysis. Methods: A literature search across major databases was conducted through May 2024 to identify MR studies linking T2DM and AD. Fixed/random-effect models provided pooled odds ratios (ORs) with 95% confidence intervals (CIs), and heterogeneity was assessed with the I² statistic. For our MR analysis, we pooled genetic variants from selected studies and analyzed AD outcomes using IGAP, EADB, and UKB databases. Multiple MR methods, including inverse variance weighted (IVW) and pleiotropy–robust approaches, were applied for validation. Results: Of 271 articles, 8 MR studies were included (sample sizes: 68,905 to 788,989), all from European ancestry. Our meta-analysis found no significant causal link between T2DM and AD (OR = 1.02, 95% CI: 1.00–1.04) with moderate heterogeneity (I² = 31.3%). Similarly, our MR analysis using 512 SNPs as instrumental variables showed no significant associations in IGAP, EADB, or UKB data, which is consistent across sensitivity analyses. Conclusions: This meta-MR and MR analysis revealed no significant causal association between T2DM and AD, indicating that genetic predisposition to T2DM does not appear to causally influence AD risk, though modifiable clinical or environmental aspects of T2DM may still contribute to neurodegenerative processes. Further research should explore other mechanisms linking these conditions. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (2nd Edition))

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21 pages, 9128 KiB

Open AccessArticle

Preclinical Research on Cinnamic Acid Derivatives for the Prevention of Liver Damage: Promising Therapies for Liver Diseases

by Liseth Rubí Aldaba-Muruato, Brayan Escalante-Hipólito, Aldo Yoshio Alarcón-López, Pablo A. Martínez-Soriano, Enrique Angeles and José Roberto Macías-Pérez

Biomedicines 2025, 13(5), 1094; https://doi.org/10.3390/biomedicines13051094 - 30 Apr 2025

Abstract

Background: Liver diseases are a global health issue with an annual mortality of 80,000 patients, mainly due to complications that arise during disease progression, as effective treatments are lacking. Objectives: This study evaluated the hepatoprotective effects of two derivatives of cinnamic acid, LQM717 [...] Read more.

Background: Liver diseases are a global health issue with an annual mortality of 80,000 patients, mainly due to complications that arise during disease progression, as effective treatments are lacking. Objectives: This study evaluated the hepatoprotective effects of two derivatives of cinnamic acid, LQM717 and LQM755, in a murine model of acute liver damage induced by carbon tetrachloride (CCl_4, 4 g/kg, single dose p.o.). Methods: Male Wistar rats were pretreated with five doses of LQM717 (20 mg/kg i.p.) or LQM755 (equimolar dose), starting 2 days before inducing hepatotoxic damage with CCl₄. Results: The key parameters of hepatocellular function and damage showed significant increases in ALT, ALP, GGT, and total and direct bilirubin in rats intoxicated with CCl₄, with decreased liver glycogen and serum albumin. Macroscopic and microscopic liver examinations revealed reduced inflammation, necrosis, and steatosis in animals pretreated with LQM717 or LQM755. Hepatomegaly was observed only in the LQM717 + CCl₄ group. LQM755 statistically provided partial protection against increases in ALT and ALP and completely prevented elevations in GGT and total and direct bilirubin. LQM755 completely prevented albumin reduction, while LQM717 only partially prevented it. Both compounds partially prevented glycogen depletion. Bioinformatic analysis identified 32 potential liver protein targets for LQM717 and 36 for LQM755. Conclusions: These findings suggest that LQM717 and LQM755 have significant hepatoprotective effects against CCl₄-induced acute liver injury, providing information for future studies in other acute and chronic models, as well as to elucidate their mechanisms of action. Full article

(This article belongs to the Special Issue Hepatotoxicity: From Pathology to Novel Therapeutic Approaches (2nd Edition))

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11 pages, 1962 KiB

Open AccessArticle

Predictors of Poor Long-Term Outcomes in Patients with Newly Diagnosed Asymptomatic Cardiac Sarcoidosis: A Cardiovascular Magnetic Resonance Study

by Nicoleta Nita, Dominik Felbel, Rima Melnic, Michael Paukovitsch, Wolfgang Rottbauer, Dominik Buckert and Johannes Mörike

Biomedicines 2025, 13(5), 1093; https://doi.org/10.3390/biomedicines13051093 - 30 Apr 2025

Abstract

Background: The prevalence of patients with cardiac sarcoidosis (CS) diagnosed at a subclinical stage has increased; however, their long-term outcomes are not well known. Objectives: To investigate the incidence and predictors of adverse long-term outcomes in newly diagnosed patients with asymptomatic CS. [...] Read more.

Background: The prevalence of patients with cardiac sarcoidosis (CS) diagnosed at a subclinical stage has increased; however, their long-term outcomes are not well known. Objectives: To investigate the incidence and predictors of adverse long-term outcomes in newly diagnosed patients with asymptomatic CS. Methods: Forty-three patients with newly diagnosed asymptomatic CS and comprehensive baseline evaluation with cardiovascular magnetic resonance (CMR) were studied. Asymptomatic CS was defined as CS in patients with biopsy-proven extracardiac sarcoidosis without cardiac symptoms but with abnormalities on CMR or positron emission tomography according to Heart Rhythm Society criteria. The primary endpoint was a composite of all-cause mortality, new ventricular arrhythmia or an atrioventricular block requiring cardiac device implantation, and hospitalization for heart failure. Results: Patients had a mean age of 56 ± 11 years and presented with normal left ventricular (LV) ejection fraction (58 ± 4%). A total of 44.2% of patients reached the composite endpoint during 5 years of follow-up. Patients with the primary endpoint were predominantly female (73.7%) and had a significantly higher prevalence of right ventricular (RV) involvement compared to patients without the primary endpoint (RV late gadolinium enhancement (LGE) in 26.3% vs. 4.2%, p = 0.037). In multivariate regression analysis, extensive LV LGE (HR 1.61, 95% CI 1.16–2.04, p = 0.004) and impaired RV global longitudinal strain (GLS) at baseline (HR 0.46, 95% CI 0.24–0.68, p = 0.015) were significantly predictive of the primary endpoint, whereas treatment with corticosteroids after CS diagnosis was significantly associated with improved outcomes (HR 7.69, 95% CI 1.11–11.11, p = 0.044). Conclusions: Newly diagnosed patients with asymptomatic CS have a significant incidence of adverse outcomes after 5 years of follow-up. The extent of LV LGE and impaired RV GLS at baseline predict poor long-term outcomes in asymptomatic CS. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnosis, and Treatment of Cardiomyopathy)

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13 pages, 4652 KiB

Open AccessArticle

MiR-27b-3p Reduces the Efficacy of Propranolol in the Treatment of Infantile Hemangioma by Inhibiting the Expression of Apaf-1

by Jing Li, Yifei Zhu, Linyang Xie, Sina Ahmadi, Chonghao Yao, Hao Cui, Xuteng Kang, Junbo Tu and Sijia Na

Biomedicines 2025, 13(5), 1092; https://doi.org/10.3390/biomedicines13051092 - 30 Apr 2025

Abstract

Objective: To explore the role and mechanism of miR-27b-3p in treating infantile hemangiomas (IHs) with propranolol and to clarify the cause of the poor efficacy of propranolol in IHs. Methods: Human umbilical vein endothelial cells (HUVECs) were used as the research [...] Read more.

Objective: To explore the role and mechanism of miR-27b-3p in treating infantile hemangiomas (IHs) with propranolol and to clarify the cause of the poor efficacy of propranolol in IHs. Methods: Human umbilical vein endothelial cells (HUVECs) were used as the research model and were treated with 0, 15, 30, 45, 60, and 90 μM of propranolol to explore the best concentration. RNA interference technology was used to regulate the expression of miR-27b-3p. CCK-8, TUNEL, and flow cytometry detected cell proliferation and apoptosis levels. Real-time PCR was used to detect the expression of miR-27b-3p and apoptosis pathway-related mRNA, and Western blotting was used to detect the expression of apoptosis-related proteins. The target relationship between miR-27b-3p and Apaf-1 was analyzed using a double Luciferase report. Results: The most significant inhibitory effect on cell activity of propranolol is at a dose of 30 μM. After propranolol treatment, the expression of miR-27b-3p was downregulated, and the expression of the apoptotic factors Apaf-1, PARP, caspase-9, and caspase-3 was upregulated, which was consistent with the results after the deletion of miR-27b-3p. However, after upregulation of miR-27b-3p, the level of and the expression of apoptotic factors was inhibited. “targetscan.org” gene database analysis found that miR-27b-3p matched the 3′-UTR of Apaf-1 mRNA, and luciferase results showed that miR-27b-3p had a targeted relationship with Apaf-1. Conclusions: The miR-27b-3p target inhibits the expression of Apaf-1, reduces the level of endothelial cell apoptosis, and interferes with the therapeutic effect of propranolol. Full article

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

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18 pages, 593 KiB

Open AccessReview

Closed-Loop Spinal Cord Stimulation in Chronic Pain Management: Mechanisms, Clinical Evidence, and Emerging Perspectives

by Nicholas Mangano, Andrew Torpey, Catherine Devitt, George A. Wen, Christopher Doh and Abhishek Gupta

Biomedicines 2025, 13(5), 1091; https://doi.org/10.3390/biomedicines13051091 - 30 Apr 2025

Abstract

Background: Chronic pain remains a major clinical challenge, which is often resistant to conventional treatments. Spinal cord stimulation has been used for decades to manage refractory pain, traditionally relying on open-loop systems with fixed-output stimulation. However, these systems fail to account for physiological [...] Read more.

Background: Chronic pain remains a major clinical challenge, which is often resistant to conventional treatments. Spinal cord stimulation has been used for decades to manage refractory pain, traditionally relying on open-loop systems with fixed-output stimulation. However, these systems fail to account for physiological variability, leading to inconsistent pain relief. Closed-loop spinal cord stimulation represents a significant advancement by utilizing evoked compound action potentials to continuously modulate stimulation intensity in real-time, ensuring more stable and effective pain management. Methods: A comprehensive literature review was conducted using PubMed and ClinicalTrials.gov to identify and synthesize relevant published and ongoing studies with a focus on open-loop spinal cord stimulation for managing lower back pain. Results: Clinical trials, including the Avalon and Evoke studies, have demonstrated that closed-loop spinal cord stimulation provides superior pain relief, functional improvement, and reduced opioid dependence compared to traditional open-loop systems. Patients receiving closed-loop stimulation reported significantly higher rates of sustained pain reduction, improved quality of life, and fewer complications related to overstimulation. Emerging studies suggest its potential for conditions beyond back pain, such as neuropathic pain, cancer-related pain, and Raynaud’s phenomenon. Furthermore, cost-effectiveness analyses indicate that closed-loop spinal cord stimulation is a more economically viable treatment option compared to conventional medical management and open-loop systems. Conclusions: Closed-loop spinal cord stimulation represents a transformative development in neuromodulation, offering personalized and adaptive pain management that is distinct from open-loop spinal cord stimulation. Further research is warranted to explore its long-term durability, broader applications, and integration with emerging technologies in pain management. Full article

(This article belongs to the Special Issue Mechanisms and Pharmacological Targets for Pain)

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