Current Issues in Molecular Biology

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18 pages, 3588 KiB

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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

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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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29 pages, 1210 KiB

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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

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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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13 pages, 561 KiB

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T Cell Repertoire Analysis as a Molecular Signature of the Spectrum of T-LGL Lymphoproliferative Disorders: Tracing the Literature

by Evangelia Stalika and Ioannis Tsamesidis

Curr. Issues Mol. Biol. 2025, 47(4), 264; https://doi.org/10.3390/cimb47040264 - 8 Apr 2025

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Abstract

CD3⁺ CD8⁺ CD57⁺ mono-, oligo-, and poly-clonal expansions, both idiopathic and clinically related diseases, including as autoimmunity, viral infections, post-transplant, and hematologic malignancies, can cause T large granular lymphocyte (T-LGL) lymphoproliferative disorders. It is yet unknown if this variability is [...] Read more.

CD3⁺ CD8⁺ CD57⁺ mono-, oligo-, and poly-clonal expansions, both idiopathic and clinically related diseases, including as autoimmunity, viral infections, post-transplant, and hematologic malignancies, can cause T large granular lymphocyte (T-LGL) lymphoproliferative disorders. It is yet unknown if this variability is a result of a dynamic process of cytotoxic T cell responses to exoantigens and autoantigens. The major aim of this review is to gather evidence from the literature in order to further highlight the possible pathogenetic mechanism that may underly the above clinical entities. Major research findings include the following: (i) pronounced skewing of the TRBV repertoire; (ii) existence of more than one immunodominant clonotype; (iii) persistent clonotypes in different timepoints albeit with fluctuating frequencies (clonal drift); and (iv) shared (‘public’) clonotypes between cases and the public databases, further suggesting a limited number of antigens implicated in pathogenesis of T-LGL cases. However, there is no clear distinction between polyclonal, oligoclonal, and monoclonal T-LGL lymphoproliferative conditions; rather, the progression from a polyclonal cytotoxic response to the emergence of T-LGL leukemia is slow. In the ontogeny and evolution of T-LGL leukemia, repertoire limits, public clonotypes, and clonal drift all clearly show selection by limited (perhaps shared) antigens. Full article

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

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25 pages, 3464 KiB

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Different Species of Bats: Genomics, Transcriptome, and Immune Repertoire

by Huifang Wang, Hao Zhou and Xinsheng Yao

Curr. Issues Mol. Biol. 2025, 47(4), 252; https://doi.org/10.3390/cimb47040252 - 7 Apr 2025

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Abstract

Bats are the only mammals with the ability to fly and are the second largest order after rodents, with 20 families and 1213 species (over 3000 subspecies) and are widely distributed in regions around the world except for Antarctica. What makes bats unique [...] Read more.

Bats are the only mammals with the ability to fly and are the second largest order after rodents, with 20 families and 1213 species (over 3000 subspecies) and are widely distributed in regions around the world except for Antarctica. What makes bats unique are their biological traits: a tolerance to zoonotic infections without getting clinical symptoms, long lifespans, a low incidence of tumors, and a high metabolism. As a result, they are receiving increasing attention in the field of life sciences, particularly in medical research. The rapid advancements in sequencing technology have made it feasible to comprehensively analyze the diverse biological characteristics of bats. This review comprehensively discusses the following: (1) The assembly and annotation overview of 77 assemblies from 54 species across 11 families and the transcriptome sequencing overview of 42 species from 7 families, focused on a comparative analysis of genomic architecture, sensory adaptations (auditory, visual, and olfactory), and immune functions. Key findings encompass marked interspecies divergence in genome size, lineage-specific expansions/contractions of immune-related gene families (APOBEC, IFN, and PYHIN), and sensory gene adaptations linked to ecological niches. Notably, echolocating bats exhibited convergent evolution in auditory genes (SLC26A5 and FOXP2), while fruit-eating bats displayed a degeneration of vision-associated genes (RHO), reflecting trade-offs between sensory specialization and ecological demands. (2) The annotation of the V (variable), D (diversity), J (joining), and C (constant) gene families in the TR and IG loci of 12 species from five families, with a focus on a comparative analysis of the differences in TR and IG genes and CDR3 repertoires between different bats and between bats and other mammals, provides us with a deeper understanding of the development and function of the immune system in organisms. Integrated genomic, transcriptomic, and immune repertoire analyses reveal that bats employ distinct antiviral strategies, primarily mediated by enhanced immune tolerance and suppressed inflammatory responses. This review provides foundational information, collaboration directions, and new perspectives for various laboratories conducting basic and applied research on the vast array of bat biology. Full article

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

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17 pages, 860 KiB

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Signaling Mechanism of Budding, Proliferation, and Tissue Regeneration in Cnidaria

by Jie Lv, Jinhong Chen, Liangzhi Li, Xiaoyu Geng, Bingbing Li, Mingke Wang and Jishun Yang

Curr. Issues Mol. Biol. 2025, 47(4), 219; https://doi.org/10.3390/cimb47040219 - 24 Mar 2025

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Abstract

Phylum Cnidaria occupies an early branching position in the evolution of eukaryotes, establishing both close and distant relationships with most other eukaryotic metazoans. Budding encompasses the complete processes of cell proliferation, differentiation, and tissue regeneration, making it an ideal model for exploring various [...] Read more.

Phylum Cnidaria occupies an early branching position in the evolution of eukaryotes, establishing both close and distant relationships with most other eukaryotic metazoans. Budding encompasses the complete processes of cell proliferation, differentiation, and tissue regeneration, making it an ideal model for exploring various aspects of cellular function and evolution. Additionally, budding serves as the primary reproductive method for increasing the cnidarian population. This asexual reproductive phase is critical for managing and mitigating cnidarian outbreaks. This paper summarizes the common factors influencing budding, the signaling pathways involved and their associated functions, and the methodologies employed in relevant research, providing a theoretical foundation for the prevention and control of cnidarian populations. Full article

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

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18 pages, 583 KiB

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Adaptations of the Genus Bradyrhizobium to Selected Elements, Heavy Metals and Pesticides Present in the Soil Environment

by Joanna Banasiewicz, Aleksandra Gumowska, Agata Hołubek and Sławomir Orzechowski

Curr. Issues Mol. Biol. 2025, 47(3), 205; https://doi.org/10.3390/cimb47030205 - 18 Mar 2025

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Abstract

Rhizobial bacteria perform a number of extremely important functions in the soil environment. In addition to fixing molecular nitrogen and transforming it into a form available to plants, they participate in the circulation of elements and the decomposition of complex compounds present in [...] Read more.

Rhizobial bacteria perform a number of extremely important functions in the soil environment. In addition to fixing molecular nitrogen and transforming it into a form available to plants, they participate in the circulation of elements and the decomposition of complex compounds present in the soil, sometimes toxic to other organisms. This review article describes the molecular mechanisms occurring in the most diverse group of rhizobia, the genus Bradyrhizobium, allowing these bacteria to adapt to selected substances found in the soil. Firstly, the adaptation of bradyrhizobia to low and high concentrations of elements such as iron, phosphorus, sulfur, calcium and manganese was shown. Secondly, the processes activated in their cells in the presence of heavy metals such as lead, mercury and arsenic, as well as radionuclides, were described. Additionally, due to the potential use of Bradyrhziobium as biofertilizers, their response to pesticides commonly used in agriculture, such as glyphosate, sulfentrazone, chlorophenoxy herbicides, flumioxazine, imidazolinone, atrazine, and insecticides and fungicides, was also discussed. The paper shows the great genetic diversity of bradyrhizobia in terms of adapting to variable environmental conditions present in the soil. Full article

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

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16 pages, 1944 KiB

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A Comprehensive Review Exploring the Role of Bone Morphogenetic Proteins [BMP]: Biological Mechanisms

by Akanksha A. Kalal and Satyajit Mohapatra

Curr. Issues Mol. Biol. 2025, 47(3), 156; https://doi.org/10.3390/cimb47030156 - 27 Feb 2025

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Abstract

Bone morphogenetic proteins (BMPs) belong to the TGF-β family. They perform diverse roles in development, osteogenesis, and vasculogenesis. BMPs have crucial functions in embryonic development and regulate the specialization of various cell types. The dysregulation of BMP activity at various stages in signal [...] Read more.

Bone morphogenetic proteins (BMPs) belong to the TGF-β family. They perform diverse roles in development, osteogenesis, and vasculogenesis. BMPs have crucial functions in embryonic development and regulate the specialization of various cell types. The dysregulation of BMP activity at various stages in signal transduction is associated with a diverse range of human diseases. It is not surprising that BMPs also have a role in tumor formation and control the progression of cancer through different phases. Nevertheless, their specific roles remain ambiguous and the findings regarding this have been inconsistent. The objective of this review is to highlight the important functions of BMP ligands, receptors, and signaling mediators and the subsequent effects on final cellular responses resulting from these signaling modalities. This review elucidates the dysregulation of BMPs identified in various cancer types, which serves as a predictive sign for favorable results in cancer therapy. Alterations in the BMP pathway can represent a crucial milestone in the genetic and molecular mechanisms that facilitate cancer formation. This review has shown that alterations in certain components of the BMP pathway are evident in various tumor forms, including breast, gastric, colorectal, and myeloma cancer. This review reinforces the conclusion that BMPs exert both beneficial and detrimental effects on cancer biology. Collectively, these findings indicate that BMPs serve multiple functions in cancer; therefore, directing therapeutic efforts to focus on BMP may be a highly effective method for treating several cancers. Full article

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

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12 pages, 831 KiB

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Research Progress on the Relationship Between PRPF8 and Cancer

by Guoqing Huang, Dandan Wang and Jiaying Xue

Curr. Issues Mol. Biol. 2025, 47(3), 150; https://doi.org/10.3390/cimb47030150 - 26 Feb 2025

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Abstract

Alternative splicing (AS) plays a crucial role in regulating gene expression and protein diversity, influencing both normal cellular function and pathological conditions, including cancer. Protein pre-mRNA processing factor 8 (PRPF8), a core component of the spliceosome, is integral to the splicing process, ensuring [...] Read more.

Alternative splicing (AS) plays a crucial role in regulating gene expression and protein diversity, influencing both normal cellular function and pathological conditions, including cancer. Protein pre-mRNA processing factor 8 (PRPF8), a core component of the spliceosome, is integral to the splicing process, ensuring accurate gene transcription and spliceosome assembly. Disruptions in PRPF8 function are linked to a variety of cancers, as mutations in this gene can induce abnormal splicing events that contribute to tumorigenesis, metastasis, and drug resistance. This review provides an in-depth analysis of the mechanisms by which PRPF8 regulates tumorigenesis through AS, exploring its role in diverse cancer types, including breast, liver, myeloid, and colorectal cancers. Furthermore, we examine the molecular pathways associated with PRPF8 dysregulation and their impact on cancer progression. We also discuss the emerging potential of targeting PRPF8 in cancer therapy, highlighting challenges in drug development. Full article

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

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