Current Issues in Molecular Biology

28 pages, 1378 KiB

Open AccessReview

Endometriosis and Adenomyosis: From Pathogenesis to Follow-Up

by Francesco Giuseppe Martire, Eugenia Costantini, Claudia D’Abate, Giorgia Schettini, Giuseppe Sorrenti, Gabriele Centini, Errico Zupi and Lucia Lazzeri

Curr. Issues Mol. Biol. 2025, 47(5), 298; https://doi.org/10.3390/cimb47050298 - 24 Apr 2025

Abstract

Endometriosis and adenomyosis are chronic, hormone-dependent disorders. Estrogens, in particular, play a pivotal role in the pathophysiology of these conditions. Understanding the disease mechanisms, including local hyperestrogenism and reduced progesterone sensitivity, is crucial for effective management. Early diagnosis is essential for appropriate therapeutic [...] Read more.

Endometriosis and adenomyosis are chronic, hormone-dependent disorders. Estrogens, in particular, play a pivotal role in the pathophysiology of these conditions. Understanding the disease mechanisms, including local hyperestrogenism and reduced progesterone sensitivity, is crucial for effective management. Early diagnosis is essential for appropriate therapeutic intervention, with medical hormonal treatment being the first-line approach. It is important to monitor patients over time and tailor hormone therapy to individual needs in order to optimize treatment adherence. Medical therapy not only enhances patients’ quality of life but also appears to slow disease progression in terms of both extent and severity. This narrative review aims to explore all aspects of endometriosis and adenomyosis, from pathogenesis to clinical symptoms, with particular emphasis on the role of hormones and the use of medical therapies. Full article

(This article belongs to the Section Molecular Medicine)

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20 pages, 2409 KiB

Open AccessReview

The Mechanical Role of YAP/TAZ in the Development of Diabetic Cardiomyopathy

by Jun-Xian Shen, Ling Zhang, Huan-Huan Liu, Zhen-Ye Zhang, Ning Zhao, Jia-Bin Zhou, Ling-Ling Qian and Ru-Xing Wang

Curr. Issues Mol. Biol. 2025, 47(5), 297; https://doi.org/10.3390/cimb47050297 - 23 Apr 2025

Abstract

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During [...] Read more.

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During the progression of the disease, the myocardium senses surrounding mechanical cues, including extracellular matrix properties, tensile tension, shear stress, and pressure load, which significantly influence the pathological remodeling of the heart through mechanotransduction. At the molecular level, the mechanisms by which mechanical cues are sensed and transduced to mediate myocardial mechanical remodeling in DCM remain unclear. The mechanosensitive transcription factors YAP and TAZ fill this gap. This article reviews the latest findings of how YAP and TAZ perceive a wide range of mechanical cues, from shear stress to extracellular matrix stiffness. We focus on how these cues are relayed through the cytoskeleton to the nucleus, where they trigger downstream gene expression. Here, we review recent progress on the crucial role of YAP and TAZ mechanotransduction in the pathological changes observed in DCM, including myocardial fibrosis, hypertrophy, inflammation, mitochondrial dysfunction, and cell death. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

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16 pages, 3010 KiB

Open AccessArticle

Laryngeal Squamous Cell Carcinoma Is Characterized by a Stronger Expression of Nectin-4 Compared to Nectin-2

by Matej Maršić, Nives Jonjić, Maja Gligora Marković, Svjetlana Janković, Marko Velepič, Ilinko Vrebac, Lara Batičić and Tamara Braut

Curr. Issues Mol. Biol. 2025, 47(5), 296; https://doi.org/10.3390/cimb47050296 - 23 Apr 2025

Abstract

Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on [...] Read more.

Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on tissue microarray (TMA) samples derived from 31 patients who underwent total laryngectomy. The findings revealed heterogenous expression of both Nectin-2 and Nectin-4 in tumor cells and surrounding stroma, with Nectin-4 expression being significantly higher than Nectin-2 expression. Specifically, 74% of cases showed weak cytoplasmic staining for Nectin-2, while 41.93% exhibited strong cytoplasmic staining for Nectin-4. Both Nectin-2 and Nectin-4 expressions were more pronounced at the invasive tumor margins. Although no significant differences in Nectin-4 expression were observed across tumor grades (W = 83.500; z = −0.463; p = 0.658), differences in expression patterns were noted. Well-differentiated tumors (Grade 1), 80.65% of cases, showed predominantly membranous Nectin-4 staining, including in squamous epithelial cells of the mucosal surface. Conversely, in less-differentiated tumors (Grade 2 and 3), a shift toward cytoplasmic staining was evident. Specifically, 74.19% of Grade 2 tumors and 100% of Grade 3 tumors showed a predominant cytoplasmic localization of Nectin-4. This transition from membranous to cytoplasmic localization was also evident in the progression from normal superficial epithelium to malignant tissue. These observations suggest that alterations in the expression and subcellular localization of Nectin-4 may be associated with carcinogenesis and could serve as potential markers for the assessment of precancerous lesions and the aggressiveness of laryngeal tumors. Full article

(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)

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14 pages, 2650 KiB

Open AccessReview

Liposomes as Imaging Agents of Inflammation and Oxidative Stress in Bone Implants

by Delia Danila, Patricia S. Pardo, R. Devesh Kumar Misra and Aladin M. Boriek

Curr. Issues Mol. Biol. 2025, 47(5), 295; https://doi.org/10.3390/cimb47050295 - 22 Apr 2025

Abstract

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in [...] Read more.

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production costs must be addressed. Research is ongoing to improve the design and functionality of liposomes. They can potentially monitor bone implants as non-invasive imaging agents, enabling early detection of complications and timely interventions. This approach can enhance patient outcomes and extend the longevity of implants, making it a promising strategy for better patient care and implant success. Full article

(This article belongs to the Special Issue Molecular Research on Free Radicals and Oxidative Stress)

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14 pages, 8775 KiB

Open AccessArticle

Enhanced Bioactivity of Fermented Aralia cordata Extract for Glucose and Immune Modulation

by Heejong Shin, Hwapyung Kim, Gwangpyung Kim, Yikyoung Kim and Boyong Kim

Curr. Issues Mol. Biol. 2025, 47(4), 294; https://doi.org/10.3390/cimb47040294 - 21 Apr 2025

Abstract

Excessive glucose absorption is a major contributing factor of metabolic disorders that necessitates effective therapeutic strategies. This study investigates the potential of fermented Aralia cordata extract (FACE) in regulating glucose transport and immune responses under high-glucose stress conditions. Caco-2 intestinal cells and L [...] Read more.

Excessive glucose absorption is a major contributing factor of metabolic disorders that necessitates effective therapeutic strategies. This study investigates the potential of fermented Aralia cordata extract (FACE) in regulating glucose transport and immune responses under high-glucose stress conditions. Caco-2 intestinal cells and L cells were treated with FACE to determine effects on key glucose-regulating proteins and cytokines. FACE treatment inhibited the expression of glucose transporters SGLT1 and GLUT2 while promoting GLP-1 secretion. This effect was associated with HDAC and somatostatin suppression, along with AMPK-γ upregulation. Notably, FACE inhibited DPP-4 expression, further enhancing GLP-1 stability and function. Immunomodulatory effects also occurred, specifically FACE promotion of T lymphocyte differentiation, with a stronger influence on Th2 cell development. Additionally, FACE increased the secretion of essential molecules for immune balance and inflammation control, including antimicrobial peptides LL-37 and defensin, along with cytokines IL-4 and IL-13. These findings suggest that FACE exerts dual effects of improving glucose regulation and modulating immune responses, highlighting its potential as a novel bioactive material for managing metabolic disorders and enhancing intestinal immunity. Further research is warranted to explore its clinical applicability in therapeutic formulations. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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17 pages, 2384 KiB

Open AccessArticle

Nephroprotective Effects of Tanacetum balsamita Extract on Metabolic-Induced Renal Injury (MIRI) in Rats

by Rumyana Simeonova, Reneta Gevrenova, Lyubomir Marinov, Yonko Savov and Dimitrina Zheleva-Dimitrova

Curr. Issues Mol. Biol. 2025, 47(4), 293; https://doi.org/10.3390/cimb47040293 - 21 Apr 2025

Abstract

The progression of type 2 diabetes is associated with multiple complications, one of which is diabetic nephropathy (DN). This study aimed at investigating the nephroprotective potential of two doses 150 mg/kg and 300 mg/kg of Tanacetum balsamita leaf extract (ETB) on metabolic-induced renal [...] Read more.

The progression of type 2 diabetes is associated with multiple complications, one of which is diabetic nephropathy (DN). This study aimed at investigating the nephroprotective potential of two doses 150 mg/kg and 300 mg/kg of Tanacetum balsamita leaf extract (ETB) on metabolic-induced renal injury (MIRI) in rats. Markers of renal oxidative stress and antioxidant defense, histopathology, serum biochemistry, and urinalysis were measured. Blood glucose level and arterial blood pressure were assessed weekly for the experimental period of eight weeks. ETB at a high dose significantly decreased the blood glucose levels and mildly lowered systolic pressure in diabetic rats. In the kidney, ETB restored the antioxidant marker malondialdehyde, reduced glutathione, and markedly increased enzymatic activity related to GSH turnover by 46% (GPx), 22% (GR), 32% (GST), and 96% (SOD). ETB reduced elevated urea and creatinine levels and alleviated the proteinuria along with other urinalysis parameters. Histopathological examination of the kidney supported the observed protective effects. Both doses of the ETB ameliorated most of the investigated parameters similarly to positive controls enalapril and acarbose. ETB benefits on MIRI-induced damages could be associated with high levels of mono- and dicaffeoylquinic acids together with a series of methoxylated flavones and flavonols, which may hold significance for its antidiabetic and nephroprotective activity. Full article

(This article belongs to the Special Issue Molecular Insights into Food-Derived Natural Products and Their Biological Activities—2nd Edition)

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13 pages, 571 KiB

Open AccessArticle

In Silico Design of Quantitative Polymerase Chain Reaction (qPCR) Assay Probes for Prostate Cancer Diagnosis, Prognosis, and Personalised Treatment

by Trevor Kenneth Wilson and Oliver Tendayi Zishiri

Curr. Issues Mol. Biol. 2025, 47(4), 292; https://doi.org/10.3390/cimb47040292 - 19 Apr 2025

Abstract

Prostate cancer is one of the world’s leading causes of cancer-related mortalities. There are several diagnostic tools and treatment plans readily available, such as prostate-specific antigen (PSA) tests and androgen deprivation therapy (ADT). However, these all come with their setbacks. Therefore, alternatives must [...] Read more.

Prostate cancer is one of the world’s leading causes of cancer-related mortalities. There are several diagnostic tools and treatment plans readily available, such as prostate-specific antigen (PSA) tests and androgen deprivation therapy (ADT). However, these all come with their setbacks. Therefore, alternatives must be developed to assist those patients for whom standardised treatment does not work. There are many genes whose mutations lead to prostate cancer development and progression. These mutations may also lead to higher resistance/vulnerability to specific therapies. In this in silico study, four genes, AR, ATM, PTEN, and TP53, were assessed, and mutations were chosen for qPCR primer and probe design. A total of 28 mutations were selected from the four genes, with PTEN (13) making up the majority of the mutations, followed by TP53 (six), then ATM (five), and finally, AR (four). All primer/probe combinations fall within the desired ranges for this study and provide valuable additions to prostate cancer’s diagnostic/prognostic landscape. These assays will require further experimental validation, but they are the first step toward a better future in the fight against this horrible disease. Full article

(This article belongs to the Section Molecular Medicine)

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48 pages, 1332 KiB

Open AccessReview

The Inflammatory Link of Rheumatoid Arthritis and Thrombosis: Pathogenic Molecular Circuits and Treatment Approaches

by Theodora Adamantidi, Maria Stavroula Pisioti, Sofia Pitsouni, Chatzikamari Maria, Karamanis Georgios, Vasiliki Dania, Nikolaos Vordos, Xenophon Krokidis and Alexandros Tsoupras

Curr. Issues Mol. Biol. 2025, 47(4), 291; https://doi.org/10.3390/cimb47040291 - 18 Apr 2025

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation that primarily affects the joints but can also involve extra-articular organs. Its multifactorial etiology remains incompletely understood, necessitating further investigation into its underlying mechanisms. The primary therapeutic goal in RA management [...] Read more.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation that primarily affects the joints but can also involve extra-articular organs. Its multifactorial etiology remains incompletely understood, necessitating further investigation into its underlying mechanisms. The primary therapeutic goal in RA management is to achieve disease remission or maintain low RA activity to prevent long-term morbidity. RA therapies aim to mitigate joint damage, reduce disability, and prevent systemic complications such as cardiovascular diseases. In addition to pharmacological treatments, non-pharmacological interventions—including physiotherapy, occupational therapy, and lifestyle modifications such as smoking cessation, regular exercise, and adherence to a balanced diet—play a crucial role in managing the disease. Beyond joint inflammation, RA has been strongly associated with an increased risk of thrombosis, contributing significantly to both morbidity and mortality. The link between RA and thrombotic events arises from a complex interplay of inflammatory pathways, endothelial dysfunction, and coagulation abnormalities. This review provides an in-depth analysis of the mechanisms driving the association between thrombo-inflammatory manifestations and the incidence of RA, the impact of RA treatment on thrombosis prevalence, and potential therapeutic strategies for managing both conditions concurrently. By integrating recent advancements in rheumatoid arthritis (RA) pathophysiology and thrombo-inflammatory research, this paper provides a comprehensive resource on the inflammatory link between RA and thrombosis while discussing and comparing current and emerging treatment approaches. Further investigation into these mechanisms could facilitate the development of targeted therapies that reduce the risk of thrombosis in patients with RA. Full article

(This article belongs to the Special Issue Molecular Research in Osteoarthritis and Osteoarticular Diseases)

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18 pages, 3588 KiB

Open AccessReview

FNIP1 Deficiency: Pathophysiology and Clinical Manifestations of a Rare Syndromic Primary Immunodeficiency

by Samuele Roncareggi, Brian M. Iritani and Francesco Saettini

Curr. Issues Mol. Biol. 2025, 47(4), 290; https://doi.org/10.3390/cimb47040290 - 18 Apr 2025

Abstract

Folliculin-interacting protein 1 (FNIP1) is a key regulator of cellular metabolism and immune homeostasis, integrating nutrient signaling with proteostasis. FNIP1 forms a complex with folliculin (FLCN) to regulate the mechanistic target of rapamycin complex 1 (mTORC1), functioning as a GTPase-activating protein (GAP) for [...] Read more.

Folliculin-interacting protein 1 (FNIP1) is a key regulator of cellular metabolism and immune homeostasis, integrating nutrient signaling with proteostasis. FNIP1 forms a complex with folliculin (FLCN) to regulate the mechanistic target of rapamycin complex 1 (mTORC1), functioning as a GTPase-activating protein (GAP) for RagC/D. Additionally, FNIP1 interacts with heat shock protein 90 (HSP90) and undergoes phosphorylation, glycosylation, and ubiquitination, which dynamically regulate its stability and function. Evidence from murine models suggests that FNIP1 loss disrupts immune cell development and mitochondrial homeostasis. However, FNIP1 deficiency in humans remains incompletely characterized, and its full phenotypic spectrum is likely underestimated. Notably, FNIP1-deficient patients exhibit immunological and hematological abnormalities, immune dysregulation, and metabolic perturbations, emphasizing its role in cellular adaptation to stress. Understanding the mechanistic basis of FNIP1 dysfunction in human tissues will be critical for delineating its contributions to immune and metabolic disorders and identifying targeted interventions. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2025)

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6 pages, 182 KiB

Open AccessEditorial

Editorial for Special Issue “Phytochemicals in Cancer Chemoprevention and Treatment”

by Wojciech Trybus, Ewa Trybus and Aneta Węgierek-Ciuk

Curr. Issues Mol. Biol. 2025, 47(4), 289; https://doi.org/10.3390/cimb47040289 - 18 Apr 2025

Abstract

Despite significant progress in the treatment of cancer patients, modern oncological therapy faces numerous challenges that are primarily related to the lack of response to treatment caused by the resistance of cancer cells to chemotherapeutics [...] Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

21 pages, 18989 KiB

Open AccessArticle

In Silico Identification of Potential Antagonists Targeting the HPV16 E2-E1 Interaction: A Step Toward Novel Therapeutics for Cervical Cancer

by Jesús Alonso Gandara-Mireles, Verónica Loera Castañeda, Julio Cesar Grijalva Ávila, Ignacio Villanueva Fierro, Cynthia Mora Muñoz, Hugo Payan Gándara, Guadalupe Antonio Loera Castañeda, Leslie Patrón Romero and Horacio Almanza Reyes

Curr. Issues Mol. Biol. 2025, 47(4), 288; https://doi.org/10.3390/cimb47040288 - 18 Apr 2025

Abstract

Human papillomavirus (HPV) infection is the most prevalent sexually transmitted disease, and a primary cause of persistent infection leading to cervical cancer (CC). CC remains one of the most common malignancies among women worldwide, with approximately 660,000 new cases and 350,000 deaths annually. [...] Read more.

Human papillomavirus (HPV) infection is the most prevalent sexually transmitted disease, and a primary cause of persistent infection leading to cervical cancer (CC). CC remains one of the most common malignancies among women worldwide, with approximately 660,000 new cases and 350,000 deaths annually. In Mexico, this cancer accounts for 13.9% of female deaths. Currently, no antiviral treatment exists for HPV infection. Available therapies for dysplasia and CC focus on the destruction or surgical removal of infected tissue using cytotoxic agents. While the prophylactic HPV vaccine effectively prevents new infections, it does not benefit the millions already infected, underscoring the urgent need for novel therapeutic strategies. This study aimed to identify potential antagonists for the interaction between the HPV16 E2 and E1 proteins through in silico screening. A virtual screening was performed targeting the TAD of the HPV16 E2 protein (PDB ID: 1DTO) using the Maybridge HitFinder™ small molecule library. Six molecules with the best binding energies were identified: 11419, 11829, 10756, 10708, 10632, and 10726. Among these, molecules 10756, 10708, 10632, and 10726 demonstrated promising potential as antagonists, interacting with Tyr19 and/or Glu39 residues. These findings highlight potent therapeutic candidates against HPV-related diseases. Full article

(This article belongs to the Special Issue Molecular Biology in Drug Design and Precision Therapy)

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29 pages, 1210 KiB

Open AccessReview

Recent Advances in Bone Tissue Engineering: Enhancing the Potential of Mesenchymal Stem Cells for Regenerative Therapies

by Milena Kostadinova, Miryana Raykovska, Radoil Simeonov, Stephan Lolov and Milena Mourdjeva

Curr. Issues Mol. Biol. 2025, 47(4), 287; https://doi.org/10.3390/cimb47040287 - 17 Apr 2025

Abstract

Bone tissue engineering (BTE) has emerged as a promising strategy for addressing bone defects and disorders that cannot be repaired through traditional methods. This field leverages the potential of various biomaterials, cells, and bioactive factors to promote bone regeneration. Mesenchymal stem cells (MSCs) [...] Read more.

Bone tissue engineering (BTE) has emerged as a promising strategy for addressing bone defects and disorders that cannot be repaired through traditional methods. This field leverages the potential of various biomaterials, cells, and bioactive factors to promote bone regeneration. Mesenchymal stem cells (MSCs) have gained significant attention due to their osteogenic potential, which can be enhanced through osteoinductive factors. Osteoinductive factors, including growth factors like BMPs, TGF-β, VEGF, and IGF, play a crucial role in stimulating the osteodifferentiation process, thereby promoting bone regeneration. Furthermore, bioprinting technologies have opened new avenues for precisely designing scaffolds that can mimic the native bone architecture and provide a conducive environment for MSC differentiation. The integration of bioprinting with mesenchymal stem cells and osteoinductive factors has the potential to revolutionize regenerative therapies by allowing for the creation of patient-specific bone grafts. This review highlights the latest developments in MSC-based therapies, the role of osteoinductive factors, and the impact of bioprinting in advancing BTE. It also discusses future directions for improving the efficacy and clinical translation of these technologies. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2025)

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18 pages, 1315 KiB

Open AccessReview

FGFRL1: Structure, Molecular Function, and Involvement in Human Disease

by Lina Guan, Li Feng, Chaoli Wang and Yongen Xie

Curr. Issues Mol. Biol. 2025, 47(4), 286; https://doi.org/10.3390/cimb47040286 - 17 Apr 2025

Abstract

FGFRL1 (fibroblast growth factor receptor-like 1) is a newly identified member of the FGFR family. Its extracellular domain resembles the four conventional FGFRs, while its intracellular part lacks the tyrosine kinase domain necessary for FGF-mediated signal transduction. At first, it was only considered [...] Read more.

FGFRL1 (fibroblast growth factor receptor-like 1) is a newly identified member of the FGFR family. Its extracellular domain resembles the four conventional FGFRs, while its intracellular part lacks the tyrosine kinase domain necessary for FGF-mediated signal transduction. At first, it was only considered a “decoy receptor”. However, recent studies have demonstrated that FGFRL1 is a multifunctional molecule involved in prenatal and postnatal growth of cartilage and osteogenesis, the development of embryonic kidney and diaphragm, the modulation of cellular biological behaviors, and cell signal transduction. The functional abnormalities of FGFRL1 contribute to human diseases including congenital disease, hypertension, osteoporosis, degenerative diseases of the central nervous system, and different kinds of tumors. The present review summarizes the research progress of FGFRL1, especially its subcellular location, molecular function, and associated human disease. These data may offer valuable resources for further studying the molecular function of FGFRL1 and disclosing the mechanism of its related human diseases. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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25 pages, 370 KiB

Open AccessReview

The Expanding Role of GLP-1 Receptor Agonists: Advancing Clinical Outcomes in Metabolic and Mental Health

by Mohamad Al Qassab, Mohammad Mneimneh, Ahmad Jradi, Bassem Derbas, Dana Dabboussi, Justine Khoury Baini, Nadia Katrib, Nadim Chaarani, Philippe Attieh, Amjad Kanaan, Frederic Harb, Sami Azar and Hilda E. Ghadieh

Curr. Issues Mol. Biol. 2025, 47(4), 285; https://doi.org/10.3390/cimb47040285 - 17 Apr 2025

Abstract

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as a promising therapeutic option beyond their established role in managing type 2 diabetes mellitus (T2DM) and obesity. Recent research has highlighted their beneficial effects on liver, kidney, and cardiovascular health, mediated by both [...] Read more.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as a promising therapeutic option beyond their established role in managing type 2 diabetes mellitus (T2DM) and obesity. Recent research has highlighted their beneficial effects on liver, kidney, and cardiovascular health, mediated by both direct and indirect mechanisms. In the liver, GLP-1 RAs contribute to the improvement of metabolic dysfunction-associated steatotic liver disease (MASLD) by reducing hepatic fat accumulation, inflammation, and oxidative stress. Additionally, they enhance insulin sensitivity and lipid metabolism. Similarly, in diabetic kidney disease (DKD), GLP-1 RAs exhibit renoprotective properties by mitigating inflammation, oxidative stress, and glomerular hypertension. Furthermore, they promote natriuresis and stabilize renal function. Moreover, GLP-1 RAs present significant cardiovascular benefits, including improved myocardial function, reduced atherosclerosis progression, enhanced endothelial health, and decreased major adverse cardiovascular events (MACEs). Additionally, emerging evidence suggests GLP-1 RAs may exert substantial neuropsychiatric benefits, including reductions in depressive symptoms, anxiety, substance use behaviors, and lowering the risk of Alzheimer’s disease, Parkinson’s disease, and other dementias likely mediated by the modulation of neurotransmitter systems and neuroinflammation. Genetic polymorphisms in the GLP1R gene also impact the therapeutic response, highlighting the importance of personalized medicine in optimizing GLP-1 RA efficacy. This review synthesizes preclinical and clinical evidence supporting the multifaceted effects of GLP-1 RAs across multiple organ systems, highlighting their therapeutic potential beyond glycemic control. As research advances, further exploration of their mechanisms of action and long-term clinical outcomes, safety and effectiveness across diverse patient populations will be essential in optimizing their use in treating metabolic and neuropsychiatric conditions. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

12 pages, 1832 KiB

Open AccessArticle

Increased Brain Glutathione Levels by Intranasal Insulin Administration

by Taisuke Kawashima, Wattanaporn Bhadhprasit, Nobuko Matsumura, Chisato Kinoshita and Koji Aoyama

Curr. Issues Mol. Biol. 2025, 47(4), 284; https://doi.org/10.3390/cimb47040284 - 17 Apr 2025

Abstract

Background: This paper investigates the effect of intranasal insulin administration on brain glutathione (GSH) levels and elucidates the potential mechanism by which insulin enhances antioxidant defenses in the brain. Methods: C57BL/6J mice were intranasally administered insulin (2 IU/day) or saline for 7 days. [...] Read more.

Background: This paper investigates the effect of intranasal insulin administration on brain glutathione (GSH) levels and elucidates the potential mechanism by which insulin enhances antioxidant defenses in the brain. Methods: C57BL/6J mice were intranasally administered insulin (2 IU/day) or saline for 7 days. GSH levels were measured in the brain and liver. Blood glucose concentrations and daily food intake were also monitored. Protein levels of excitatory amino acid carrier-1 (EAAC1), its interaction with glutamate transport-associated protein 3-18(GTRAP3-18), and activated AMP-activated protein kinase (AMPK) were assessed. Results: Insulin-treated mice exhibited significantly higher GSH levels in the hippocampus and midbrain compared to saline-treated controls, while no significant differences were found in liver GSH levels, blood glucose concentrations, or food intake. EAAC1 expression increased in both the cytosolic and plasma membrane fractions of insulin-treated mouse brains. Furthermore, the interaction between EAAC1 and its negative regulator, GTRAP3-18, along with activated AMPK levels, was reduced in insulin-treated mice. Conclusions: Intranasal insulin administration enhances brain GSH levels through a mechanism involving EAAC1 upregulation and reduced AMPK activation. These findings suggest that intranasal insulin could be a promising strategy for enhancing antioxidant defenses against neurodegeneration in the brain. Full article

(This article belongs to the Special Issue Molecular and Pharmacological Insights into Bioactive Compounds: Pathways to Therapeutics)

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28 pages, 339 KiB

Open AccessReview

The Role of HSP47 in Thrombotic Disorders: Molecular Mechanism and Therapeutic Potential

by Minodora Teodoru, Oana-Maria Stoia, Maria-Gabriela Vladoiu and Alexandra-Kristine Tonch-Cerbu

Curr. Issues Mol. Biol. 2025, 47(4), 283; https://doi.org/10.3390/cimb47040283 - 17 Apr 2025

Abstract

This review aims to analyze the role of heat shock protein 47 (HSP47) in thrombosis and evaluate its potential as a therapeutic target for deep vein thrombosis (DVT). A systematic literature review was conducted using PubMed, Scopus, and Web of Science to identify [...] Read more.

This review aims to analyze the role of heat shock protein 47 (HSP47) in thrombosis and evaluate its potential as a therapeutic target for deep vein thrombosis (DVT). A systematic literature review was conducted using PubMed, Scopus, and Web of Science to identify studies on HSP47, thrombosis, and collagen, selecting only relevant and methodologically rigorous articles. HSP47 regulates platelet function and collagen interaction, playing a key role in deep vein thrombosis (DVT). HSP47, known for stabilizing collagen, also improves platelet–collagen binding and thrombus formation. In addition, reduced HSP47 levels reduce platelet adhesion, resulting in reduced thrombus formation, while inhibitors that target HSP47 decrease platelet aggregation in animal models. Naturally low levels of HSP47 during prolonged immobility are also found in hibernating mammals, such as bears, and are associated with reduced formation of thrombi, indicating a possible natural mechanism of thrombo-protection. This observation could inform new therapeutic approaches. Current studies use in vitro platelet aggregation assays, flow chamber assays, and collagen binding studies to investigate the role of HSP47 in clotting. This review aims to synthesize existing evidence to better understand HSP47’s role in clot formation and explore its potential as a target for novel DVT therapies. Full article

(This article belongs to the Special Issue Cerebrovascular Diseases: From Pathogenesis to Treatment)

14 pages, 749 KiB

Open AccessReview

Molecular Mechanisms and Potential Therapeutic Targets of Ischemia–Reperfusion Injury in Kidney Transplantation

by Aaron J. Huang, Gaurav K. Sharma, Rohan Parikh, Zhaosheng Jin, Frank S. Darras and Sergio D. Bergese

Curr. Issues Mol. Biol. 2025, 47(4), 282; https://doi.org/10.3390/cimb47040282 - 17 Apr 2025

Abstract

End-stage renal disease (ESRD) is a serious and lethal disease that carries with it a high morbidity and mortality rate if left untreated. Treating ESRD is conducted via renal replacement therapy and/or kidney transplantation, with the latter being the preferred option given the [...] Read more.

End-stage renal disease (ESRD) is a serious and lethal disease that carries with it a high morbidity and mortality rate if left untreated. Treating ESRD is conducted via renal replacement therapy and/or kidney transplantation, with the latter being the preferred option given the better outcomes and quality of life for the patients. However, as ESRD rises in prevalence, kidney transplantation rates remain largely unchanged. In every kidney transplantation, ischemia–reperfusion injury (IRI) is inevitable and the effect this has on the kidney depends based on donor type. IRI works through a variety of molecular mechanisms, primarily mitochondrial oxidative stress and programmed cell death mechanisms. Given the urgency to ensure the best outcomes for these limited kidney transplants, there has been a continued effort to find various potential therapeutic mechanisms to counteract IRI preoperatively, intraoperatively, and postoperatively. These include hypothermic machine perfusion, ischemic conditioning, nanoparticle removal of free radicals, peptide-based therapies, microRNA, and more. There is an ongoing effort to find the best way to mitigate IRI in kidney transplantation and this is being achieved through a better understanding of the molecular mechanisms of IRI. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Ischemia–Reperfusion Injury)

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17 pages, 1705 KiB

Open AccessArticle

Associating Patient Responses with Drug Sensitivity in Non-Small Cell Lung Carcinoma Using an Immunoassay on Patient-Derived Cell Cultures

by Ana Podolski-Renić, Sofija Jovanović Stojanov, Dragana Marić, Jelena Dinić, Miodrag Dragoj, Ana Stepanović, Ema Lupšić, Milica Pajović, Sofija Glumac, Maja Ercegovac and Milica Pešić

Curr. Issues Mol. Biol. 2025, 47(4), 281; https://doi.org/10.3390/cimb47040281 - 17 Apr 2025

Abstract

Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique [...] Read more.

Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. Methods: We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients’ responses to therapy. We used Kaplan–Meier analysis to assess progression-free survival (PFS) differences among patient groups. Results: NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). Conclusions: A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients’ cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers. Full article

(This article belongs to the Section Molecular Medicine)

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12 pages, 250 KiB

Open AccessArticle

Evaluation of miRNA Profile and Its Relationship with Metabolic Disorders in Obese and Pre-Obese Patients

by Kürşat Kargün, Erhan Aygen, Mehmet Fatih Ebiloğlu, Naci Ömer Alayunt and Lütfiye Kadıoğlu Dalkılıç

Curr. Issues Mol. Biol. 2025, 47(4), 280; https://doi.org/10.3390/cimb47040280 - 17 Apr 2025

Abstract

Obesity is a growing global public health concern, with its prevalence rapidly increasing in Turkey, leading to severe consequences. Genetic factors, particularly mutations in structural genes and microRNAs (miRNAs) involved in gene expression regulation have been widely investigated in obesity research. This study [...] Read more.

Obesity is a growing global public health concern, with its prevalence rapidly increasing in Turkey, leading to severe consequences. Genetic factors, particularly mutations in structural genes and microRNAs (miRNAs) involved in gene expression regulation have been widely investigated in obesity research. This study aimed to explore the role of obesity-associated miRNAs and their potential interaction with vascular response alterations. A total of 60 obese and pre-obese patients and 26 age- and sex-matched healthy controls from the General Surgery Department of Fırat University Medicine School were included. The expression levels of 93 miRNAs were analyzed in 86 samples using the Fluidigm Biomark RT-PCR system, with 5S RNA as the housekeeping gene. Significant differences were observed in weight, BMI, cholesterol, triglyceride levels, and lymphocyte counts between the groups (p < 0.0001). Several miRNAs, including hsa-miR-148a-3p, hsa-miR-503-3p, hsa-miR-34a-5p, and hsa-miR-199a-3p, were significantly downregulated in obese patients. Additionally, gender-specific differences in miRNA expression were identified. These findings indicate that miRNAs play a crucial role in obesity pathophysiology and could serve as potential biomarkers and therapeutic targets for obesity treatment. Full article

(This article belongs to the Section Molecular Medicine)

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