International Journal of Molecular Sciences

19 pages, 5504 KiB

Open AccessArticle

The Impact of Bariatric Surgery on Gut Microbiota Composition and Diversity: A Longitudinal Analysis Using 16S rRNA Sequencing

by Radu Petru Soroceanu, Daniel Vasile Timofte, Sergiu Timofeiov, Vlad Ionut Vlasceanu, Madalina Maxim, Ancuta Andreea Miler, Andi Gabriel Iordache, Roxana Moscalu, Mihaela Moscalu, Irina Cezara Văcărean-Trandafir, Roxana-Maria Amărandi, Iuliu Cristian Ivanov and Alin Constantin Pînzariu

Int. J. Mol. Sci. 2025, 26(16), 7933; https://doi.org/10.3390/ijms26167933 (registering DOI) - 17 Aug 2025

Abstract

Bariatric surgery is considered the most effective treatment for obesity and its associated metabolic disorders, yet the underlying mechanisms are only partially understood. Evidence suggests that the gut microbiota plays an important role in metabolic regulation and can be significantly altered by bariatric [...] Read more.

Bariatric surgery is considered the most effective treatment for obesity and its associated metabolic disorders, yet the underlying mechanisms are only partially understood. Evidence suggests that the gut microbiota plays an important role in metabolic regulation and can be significantly altered by bariatric and metabolic procedures. This prospective, single-center study aimed to evaluate the dynamic changes in the gut microbiota composition and diversity in obese patients undergoing two types of bariatric surgery: laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB). Fecal samples were collected at three time points—before surgery (T0), and at 3 (T3) and 6 months (T6) postoperatively—and analyzed using 16S rRNA gene sequencing targeting the V3–V4 regions with Illumina technology. Significant shifts in microbial diversity and structure were observed over time, indicating a trend toward microbiota normalization post-surgery. Notable changes included a reduction in the Firmicutes/Bacteroidetes ratio and increased relative abundance of Actinobacteria, Proteobacteria, and Verrucomicrobia. These alterations occurred in parallel with improvements in body mass index (BMI) and metabolic parameters. Our findings suggest that bariatric surgery induces favorable and sustained modifications in the gut microbiota, which may contribute to its therapeutic effects in obesity management. Full article

(This article belongs to the Special Issue Interplay Between the Human Microbiome and Diseases)

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16 pages, 2171 KiB

Open AccessArticle

Inflammatory Crosstalk Between Type 2 Diabetes and Sarcopenia: Insights from In Silico Evaluation

by Cristina Russo, Maria Stella Valle, Maria Teresa Cambria and Lucia Malaguarnera

Int. J. Mol. Sci. 2025, 26(16), 7932; https://doi.org/10.3390/ijms26167932 (registering DOI) - 17 Aug 2025

Abstract

Sarcopenia and type 2 diabetes mellitus (T2DM) are chronic conditions that gradually affect the elderly, often coexisting and interacting in complex ways. Sarcopenia, which is characterized by the progressive loss of muscle mass and function, is frequently observed in individuals with T2DM. Although [...] Read more.

Sarcopenia and type 2 diabetes mellitus (T2DM) are chronic conditions that gradually affect the elderly, often coexisting and interacting in complex ways. Sarcopenia, which is characterized by the progressive loss of muscle mass and function, is frequently observed in individuals with T2DM. Although the clinical association is well known, the molecular mechanisms remain unclear. Gene expression datasets were retrieved from the Gene Expression Omnibus database. DEGs were identified using the limma package in R (R 4.4.0). Shared DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein–protein interaction networks were constructed using the STRING database and were visualized with Cytoscape. Hub genes were identified via six topological algorithms in the CytoHubba plugin. Pearson’s correlation analysis was conducted between hub genes and selected metabolic regulators. GO and KEGG enrichment analyses indicated that mitochondrial function, oxidative phosphorylation, and immune–inflammatory responses were significantly enriched. A PPI network revealed a mitochondrial hub of five key genes involved in energy metabolism, whose downregulation suggests mitochondrial dysfunction as a shared mechanism in sarcopenia and T2DM. Our results provide new insight into the molecular overlap between T2DM and sarcopenia, highlighting potential biomarkers and therapeutic targets for addressing both metabolic disruption and muscle decline. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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13 pages, 1294 KiB

Open AccessReview

VEXAS Syndrome: Genetics, Gender Differences, Clinical Insights, Diagnostic Pitfalls, and Emerging Therapies

by Salvatore Corrao, Marta Moschetti, Salvatore Scibetta, Luigi Calvo, Annarita Giardina, Ignazio Cangemi, Carmela Zizzo, Paolo Colomba and Giovanni Duro

Int. J. Mol. Sci. 2025, 26(16), 7931; https://doi.org/10.3390/ijms26167931 (registering DOI) - 17 Aug 2025

Abstract

VEXAS syndrome (Vacuoles, E1-enzyme, X-linked, Autoinflammation, and Somatic) is a recently identified late-onset autoinflammatory disorder characterized by a unique interplay between hematological and inflammatory manifestations. It results from somatic mutations in the UBA1 gene, located on the short arm of the X chromosome. [...] Read more.

VEXAS syndrome (Vacuoles, E1-enzyme, X-linked, Autoinflammation, and Somatic) is a recently identified late-onset autoinflammatory disorder characterized by a unique interplay between hematological and inflammatory manifestations. It results from somatic mutations in the UBA1 gene, located on the short arm of the X chromosome. Initially, females were considered mere carriers, with the syndrome primarily affecting males over 50. However, recent evidence indicates that heterozygous females can exhibit symptoms as severe as those seen in hemizygous males. The disease manifests as systemic inflammation, macrocytic anemia, thrombocytopenia, chondritis, neutrophilic dermatoses, and steroid-dependent inflammatory symptoms. Due to its overlap with autoimmune and hematologic disorders such as relapsing polychondritis, Still’s disease, and myelodysplastic syndromes, misdiagnosis is common. At the molecular level, VEXAS syndrome is driven by impaired ubiquitination pathways, resulting in dysregulated immune responses and clonal hematopoiesis. A key diagnostic marker is the presence of cytoplasmic vacuoles in myeloid and erythroid precursors, though definitive diagnosis requires genetic testing for UBA1 mutations. Traditional immunosuppressants and TNF inhibitors are generally ineffective, while JAK inhibitors and IL-6 blockade provide partial symptom control. Azacitidine and decitabine have shown promise in reducing disease burden, but hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, albeit with significant risks. This review provides a comprehensive analysis of VEXAS syndrome, examining its clinical features, differential diagnoses, diagnostic challenges, and treatment approaches, including both pharmacological and non-pharmacological strategies. By enhancing clinical awareness and optimizing therapeutic interventions, this article aims to bridge emerging genetic insights with practical patient management, ultimately improving outcomes for those affected by this complex and often life-threatening disease. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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13 pages, 1100 KiB

Open AccessArticle

Molecular Networking-Guided Annotation of Flavonoid Glycosides from Quercus mongolica Bee Pollen

by Yerim Joo, Eunbeen Shin, Hyunwoo Kim, Mi Kyeong Lee and Seon Beom Kim

Int. J. Mol. Sci. 2025, 26(16), 7930; https://doi.org/10.3390/ijms26167930 (registering DOI) - 17 Aug 2025

Abstract

Bee pollen is a primary and secondary metabolite-rich natural product collected by pollinators such as honeybees. Polyphenols, particularly flavonoids, are well known for their potent antioxidant activities. Numerous phytochemical and biological studies have focused on Quercus mongolica, a member of the Fagaceae [...] Read more.

Bee pollen is a primary and secondary metabolite-rich natural product collected by pollinators such as honeybees. Polyphenols, particularly flavonoids, are well known for their potent antioxidant activities. Numerous phytochemical and biological studies have focused on Quercus mongolica, a member of the Fagaceae family. However, research focusing specifically on pollen is limited. Moreover, bee pollen chemical composition varies significantly depending on its geographical origin and cultivation conditions. In this study, the flavonoid glycosides of Q. mongolica pollen were profiled using LC–MS/MS-based molecular networking, which revealed that the largest molecular cluster corresponded to flavonoid glycosides. A total of 69 flavonoid glycosides, primarily comprising 2 kaempferol derivatives, 14 quercetin derivatives, and 46 isorhamnetin derivatives, were annotated based on MS/MS fragmentation patterns, spectral library matches in GNPS (Global Natural Products Social Molecular Networking), and comparison with previously reported data. Two primary compounds, isorhamnetin 3-O-β-_D-xylopyranosyl (1→6)-β-_D-glucopyranoside and isorhamnetin-3-O-neohesperidoside, were identified by comparison with reference standards. This study offers foundational insights into the flavonoid diversity of Q. mongolica pollen, contributing to a broad understanding of its secondary metabolite profile. Full article

(This article belongs to the Special Issue Application of Natural Products in Biomedicine and Pharmacotherapy: 2nd Edition)

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18 pages, 1451 KiB

Open AccessArticle

DAOA and APOEε4 as Modifiers of Age of Onset in Autosomal-Dominant Early-Onset Alzheimer’s Disease Caused by the PSEN1 A431E Variant

by César A. Valdez-Gaxiola, Frida Rosales-Leycegui, Abigail Gaxiola-Rubio, Sofía Dumois-Petersen, Martha Patricia Gallegos-Arreola, John M. Ringman and Luis E. Figuera

Int. J. Mol. Sci. 2025, 26(16), 7929; https://doi.org/10.3390/ijms26167929 (registering DOI) - 16 Aug 2025

Abstract

While most of the Alzheimer’s disease (AD) cases are sporadic and manifest after age 65 (late-onset AD, LOAD), a subset of patients develop symptoms earlier in life (early-onset, EOAD) due to mutations in the PSEN1, PSEN2, or APP genes with an autosomal-dominant [...] Read more.

While most of the Alzheimer’s disease (AD) cases are sporadic and manifest after age 65 (late-onset AD, LOAD), a subset of patients develop symptoms earlier in life (early-onset, EOAD) due to mutations in the PSEN1, PSEN2, or APP genes with an autosomal-dominant inheritance pattern (AD-EOAD). In this study, we examined the association between age of onset (AoO) and first clinical manifestation (FCM) with the APOE and DAOA genotypes, previously described as modifiers of clinical phenotypes in LOAD and EOAD in 88 individuals clinically diagnosed with AD-EOAD due to the PSEN1 A431E variant (39 females, 49 males). We classified the population according to their genotype (APOEε2, APOEε3, and APOEε4 and DAOA G/G, G/A, and A/A) and FCM (cognitive, behavioral, motor, and memory impaired). Memory impairment was the most frequent symptom (51%), followed by motor disturbances (31.8%), cognitive symptoms other than memory (10.4%), and behavioral changes (6.8%). We found a significant association between APOE genotype and AoO (p < 0.001), with the APOEε4 allele being linked to a delayed onset (β = 4.04, SE = 1.11, p = 0.0003). Similarly, individuals with the DAOA rs2391191 A/A genotype showed a significantly later AoO compared to G/G carriers (β = 2.13, SE = 0.96, p = 0.0301). No significant association was found between APOE or DAOA genotypes and FCM. The findings suggest that both the APOEε4 allele and DAOA rs2391191 A/A genotype may act as genetic modifiers of AoO, delaying symptom onset in individuals with AD-EOAD. Further research is needed to elucidate the molecular pathways through which APOE and DAOA influence AD-EOAD progression. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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21 pages, 3177 KiB

Open AccessReview

Immunological and Inflammatory Biomarkers in the Prognosis, Prevention, and Treatment of Ischemic Stroke: A Review of a Decade of Advancement

by Marius P. Iordache, Anca Buliman, Carmen Costea-Firan, Teodor Claudiu Ion Gligore, Ioana Simona Cazacu, Marius Stoian, Doroteea Teoibaș-Şerban, Corneliu-Dan Blendea, Mirela Gabriela-Irina Protosevici, Cristiana Tanase and Maria-Linda Popa

Int. J. Mol. Sci. 2025, 26(16), 7928; https://doi.org/10.3390/ijms26167928 (registering DOI) - 16 Aug 2025

Abstract

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, [...] Read more.

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article

(This article belongs to the Section Molecular Neurobiology)

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21 pages, 7856 KiB

Open AccessArticle

Cilastatin Attenuates Acute Kidney Injury and Reduces Mortality in a Rat Model of Sepsis

by María Ángeles González-Nicolás, Blanca Humanes, Raquel Herrero, Mario Arenillas, Beatriz López, Antonio Ferruelo, José Ángel Lorente and Alberto Lázaro

Int. J. Mol. Sci. 2025, 26(16), 7927; https://doi.org/10.3390/ijms26167927 (registering DOI) - 16 Aug 2025

Abstract

Sepsis is a life-threatening condition caused by an abnormal host response to infection, leading to organ dysfunction and potentially death. Acute kidney injury (AKI) is a critical complication of sepsis. Various pathways, especially signaling through Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domain, [...] Read more.

Sepsis is a life-threatening condition caused by an abnormal host response to infection, leading to organ dysfunction and potentially death. Acute kidney injury (AKI) is a critical complication of sepsis. Various pathways, especially signaling through Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome, contribute to inflammation and tissue damage. Cilastatin, a renal dehydropeptidase I inhibitor, has shown promise in protecting against AKI induced by nephrotoxic drugs. This study assessed cilastatin’s effectiveness in preventing AKI and inflammation caused by sepsis and its impact on survival. Sepsis was induced in male Sprague-Dawley rats using the cecal ligation puncture (CLP) model, with four groups: sham (control), CLP, sham+cilastatin, and CLP+cilastatin. Cilastatin (150 mg/kg) was administered immediately and 24 h after sepsis induction. Kidney injury was evaluated 48 h later by assessing serum creatinine, blood urea nitrogen, glomerular filtration rate, proteinuria, kidney injury molecule-1 levels, and renal morphology. Inflammatory and fibrotic biomarkers, particularly related to the TLR4 and NLRP3 pathways, were also measured. Cilastatin treatment prevented kidney dysfunction, reduced inflammatory markers, and improved survival by 33%. These results suggest that cilastatin could be a beneficial therapeutic strategy for sepsis-related AKI, improving outcomes and reducing mortality. Full article

(This article belongs to the Special Issue Acute Kidney Injury: From Molecular Pathology to Therapies)

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Graphical abstract

12 pages, 528 KiB

Open AccessReview

The Antioxidant Potential of Black Tea Polyphenols in Heavy Metal Toxicity: An In Vitro Perspective

by Ewa Wnuk

Int. J. Mol. Sci. 2025, 26(16), 7926; https://doi.org/10.3390/ijms26167926 (registering DOI) - 16 Aug 2025

Abstract

Black tea is one of the most widely consumed beverages in the world, second only to water. Its properties are primarily due to the presence of polyphenols, which are associated with various effects, including antioxidant, anticancer, antiviral, and anti-inflammatory activities. These compounds include, [...] Read more.

Black tea is one of the most widely consumed beverages in the world, second only to water. Its properties are primarily due to the presence of polyphenols, which are associated with various effects, including antioxidant, anticancer, antiviral, and anti-inflammatory activities. These compounds include, among others, theaflavins (TFs) and thearubigins (TRs). The available literature provides numerous reports confirming the positive properties of these compounds. However, it is important to highlight their potential protective effects against oxidative stress induced by heavy metals. This is an important topic, given the ongoing exposure to such pollutants—resulting mainly from industrial development, among other factors. This manuscript provides a summary of the current knowledge on the properties of TFs and TRs and their effect against oxidative stress caused by heavy metals in in vitro studies. The limited amount of research in this area shows that this is still a poorly researched topic. Comparing the results obtained for epigallocatechin gallate (EGCG) from green tea, which has a similar structure to TFs and TRs suggests that they may exhibit similar or even enhanced antioxidant properties. Considering that black tea is consumed much more frequently than green tea worldwide, it is understandable that the antioxidant potential of these two compounds on cells needs to be investigated. Full article

(This article belongs to the Special Issue Advances in Anti-Inflammatory Activity of Natural Products of Plant Origin)

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26 pages, 2402 KiB

Open AccessReview

CRISPR/Cas-Mediated Optimization of Soybean Shoot Architecture for Enhanced Yield

by Nianao Li, Xi Yuan, Bei Han, Wei Guo and Haifeng Chen

Int. J. Mol. Sci. 2025, 26(16), 7925; https://doi.org/10.3390/ijms26167925 (registering DOI) - 16 Aug 2025

Abstract

Plant architecture is a crucial agronomic trait significantly impacting soybean (Glycine max) yield. Traditional breeding has made some progress in optimizing soybean architecture, but it is limited in precision and efficiency. The Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein [...] Read more.

Plant architecture is a crucial agronomic trait significantly impacting soybean (Glycine max) yield. Traditional breeding has made some progress in optimizing soybean architecture, but it is limited in precision and efficiency. The Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein (CRISPR/Cas) system, a revolutionary gene-editing technology, provides unprecedented opportunities for plant genetic improvement. This review outlines CRISPR’s development and applications in crop improvement, focusing specifically on progress regulating soybean architecture traits affecting yield, such as node number, internode length, branching, and leaf morphology. It also discusses the technical challenges for CRISPR technology in enhancing soybean architecture, including that the regulatory network of soybean plant architecture is complex and the development of multi-omics platforms helps gene mining. The application of CRISPR enables precise the regulation of gene expression through promoter editing. Meanwhile, it is also faced with technical challenges such as the editing of homologous genes caused by genome polyploidy, the efficiency of editing tools and off-target effects, and low transformation efficiency. New delivery systems such as virus-induced genome editing bring hope for solving some of these problems. The review emphasizes the great potential of CRISPR technology in breeding next-generation soybean varieties with optimized architecture to boost yield potential. Full article

(This article belongs to the Special Issue Recent Advances in Soybean Molecular Breeding)

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29 pages, 2711 KiB

Open AccessArticle

Methodological Development of a Test for Salivary Proteome Analysis Useful in Lung Cancer Screening

by Leonarda Barra, Elena Carestia, Giulia Ferri, Mohammad Kazemi, Massoumeh Ramahi, Uditanshu Priyadarshi, Velia Di Resta, Fabrizio Di Giuseppe, Renata Ciccarelli, Achille Lococo and Stefania Angelucci

Int. J. Mol. Sci. 2025, 26(16), 7924; https://doi.org/10.3390/ijms26167924 (registering DOI) - 16 Aug 2025

Abstract

Early diagnosis of lung cancer, essential for reducing its high mortality rate, is currently challenging, partly due to the lack of specific biomarkers. Here, we attempted to develop a noninvasive and potentially sensitive screening method based on the proteomic analysis of unstimulated and [...] Read more.

Early diagnosis of lung cancer, essential for reducing its high mortality rate, is currently challenging, partly due to the lack of specific biomarkers. Here, we attempted to develop a noninvasive and potentially sensitive screening method based on the proteomic analysis of unstimulated and stimulated saliva samples, collected by passive drooling and salivary swabs, respectively, from healthy heavy smokers enrolled in a nonprofit screening project. Protein content analyzed before and after sample cryopreservation for various periods and the associated two-dimensional electrophoresis revealed that protein extraction after short-term cryopreservation prevented the loss of detectable proteins. Mass spectrometric analysis of these electrophoretically resolved proteins revealed the presence of salivary proteins whose levels may be dysregulated in various types of lung cancer. Finally, in pilot experiments conducted on stimulated saliva from a patient with a lung cancer nodule, we detected altered content or selective presence of proteins involved in lung carcinogenesis, such as serpin B3 or the proteins S100A14 and aldoketoreductase-A1, respectively. While acknowledging that these findings require further validation, we believe that the use of saliva and related proteomic analyses may contribute to the identification of potential early lung cancer biomarkers, which could hopefully improve clinical management of the tumor and patient survival. Full article

(This article belongs to the Section Molecular Biology)

15 pages, 2093 KiB

Open AccessArticle

Sperm DNA Fragmentation Impairs Early Embryo Development but Is Not Predictive of Pregnancy Outcomes: Insights from 870 ICSI Cycles

by Tomasz Machałowski, Julita Machałowska, Kamil Gill, Maciej Ziętek, Małgorzata Piasecka, Grzegorz Mrugacz and Przemysław Ciepiela

Int. J. Mol. Sci. 2025, 26(16), 7923; https://doi.org/10.3390/ijms26167923 (registering DOI) - 16 Aug 2025

Abstract

Sperm DNA fragmentation (SDF) is increasingly regarded as a biomarker of male infertility, but its predictive value for intracytoplasmic sperm injection (ICSI) outcomes remains controversial. This retrospective cohort study analyzed 870 fresh single-blastocyst ICSI cycles performed between January 2023 and December 2024. SDF [...] Read more.

Sperm DNA fragmentation (SDF) is increasingly regarded as a biomarker of male infertility, but its predictive value for intracytoplasmic sperm injection (ICSI) outcomes remains controversial. This retrospective cohort study analyzed 870 fresh single-blastocyst ICSI cycles performed between January 2023 and December 2024. SDF was measured using the Sperm Chromatin Dispersion test and patients were categorized into low (SDF ≤ 20%, n = 664) and high (SDF > 20%, n = 206) groups. Higher SDF was significantly associated with reduced semen quality, lower fertilization rates, and poorer blastocyst development. In multivariable analysis, each 1% increase in SDF reduced the odds of achieving a fertilization rate > 80% by 1.6% (OR = 0.984, 95% CI: 0.971–0.997, p = 0.015) and decreased the chance of obtaining top-quality blastocysts on day 5 by 2.5% (OR = 0.975, 95% CI: 0.958–0.992, p = 0.004). A trend toward impaired day-3 embryo quality was observed (OR = 0.983, p = 0.068). No significant association was found with clinical pregnancy (OR = 0.989, p = 0.155), while the relationship with miscarriage was borderline (OR = 0.961, p = 0.053). These findings suggest that elevated SDF adversely impacts early embryological outcomes in ICSI, supporting its use as a prognostic tool during ART counseling. Full article

(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)

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23 pages, 1324 KiB

Open AccessReview

Engineered Healing: Synergistic Use of Schwann Cells and Biomaterials for Spinal Cord Regeneration

by Theo Andriot, Mousumi Ghosh and Damien D. Pearse

Int. J. Mol. Sci. 2025, 26(16), 7922; https://doi.org/10.3390/ijms26167922 (registering DOI) - 16 Aug 2025

Abstract

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection [...] Read more.

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection after SCI, with their therapeutic potential validated in clinical trials demonstrating safe and feasible transplantation in humans. Although SC transplantation has shown promising results, challenges remain, including modest graft survival, limited host integration, and restricted migration that collectively contribute to constrain efficacy. To address these limitations, biomaterial scaffolds have been explored as synergistic platforms to enhance SC delivery and function. When combined with natural or synthetic biomaterials such as hydrogels, nanofiber scaffolds, or ECM-mimetic matrices, SCs demonstrate improved survival, retention, spatial distribution, and regenerative activity. The intrinsic regenerative properties of SCs, first demonstrated in models of peripheral nerve injury, make them particularly well-suited for neural repair of the central nervous system (CNS) compared to other cell types and their effectiveness can be enhanced synergistically when combined with biomaterials. These constructs not only provide structural support but also modulate the lesion microenvironment, enhance axon growth and improve SC integration with host tissue. Combinatorial approaches incorporating biomaterials with SCs are emerging as next-generation strategies to optimize repair for clinical translation. This review focuses on current progress in SC-based therapies combined with biomaterials, highlighting key preclinical advances, clinical translation efforts, and the path forward toward effective regenerative interventions for SCI. Full article

(This article belongs to the Special Issue Biomedical Polymer Materials: Design, Synthesis or Applications)

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23 pages, 890 KiB

Open AccessReview

Functional and Structural Uterine Changes in PCOS

by Lucja Zaborowska, Joanna Maria Blok, Emilia Piotrkowicz, Steven R. Lindheim and Artur Ludwin

Int. J. Mol. Sci. 2025, 26(16), 7921; https://doi.org/10.3390/ijms26167921 (registering DOI) - 16 Aug 2025

Abstract

(1) Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders worldwide; its complex etiopathology remains poorly understood. PCOS is associated with a broad spectrum of abnormalities, including irregular menses, androgen excess, and increased risk of metabolic, endocrinological, and cardiovascular disorders. [...] Read more.

(1) Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders worldwide; its complex etiopathology remains poorly understood. PCOS is associated with a broad spectrum of abnormalities, including irregular menses, androgen excess, and increased risk of metabolic, endocrinological, and cardiovascular disorders. This narrative review focuses on structural and functional changes in the uterus associated with polycystic ovary syndrome and hyperandrogenism. (2) The review was performed by searching PubMed, Medline, Embase, Google Scholar, and Cochrane Library electronic databases on records published between 1964 and 2025. The authors included studies on (i) the uterus in clinical settings of PCOS patients, (ii) the uterus in PCOS models, and (iii) the pregnant uterus in patients with PCOS. Multiple animal and human studies describe a potential impact of PCOS on uterine blood flow, morphology, and thickness of the uterine muscle, indicating a possible functional impairment in pregnant and non-pregnant women. The scope of available knowledge regarding functional and structural uterine changes in PCOS is scarce; new studies are warranted. Future research should focus on hyperandrogenism associated with PCOS and explore the link between the morphology and function of the uterus. Full article

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

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12 pages, 1727 KiB

Open AccessReview

Comparative Effect of Conventional and Non-Conventional Over-the-Counter Treatments for Male Androgenetic Alopecia: A Network Meta-Analysis Study

by Aditya K. Gupta, Mesbah Talukder, Sharon Keene, Greg Williams and Mary A. Bamimore

Int. J. Mol. Sci. 2025, 26(16), 7920; https://doi.org/10.3390/ijms26167920 (registering DOI) - 16 Aug 2025

Abstract

The expanding literature on nutraceuticals for male androgenetic alopecia (AGA) has inadvertently created knowledge gaps on the relative efficacy of conventional and non-conventional over-the-counter (OTC) treatments. We conducted a Bayesian network meta-analysis (NMA); the outcome measure was the 24-week change in total hair [...] Read more.

The expanding literature on nutraceuticals for male androgenetic alopecia (AGA) has inadvertently created knowledge gaps on the relative efficacy of conventional and non-conventional over-the-counter (OTC) treatments. We conducted a Bayesian network meta-analysis (NMA); the outcome measure was the 24-week change in total hair density (INPLASY202570087). We determined the relative efficacy of nine active comparators—including topical minoxidil 5% and 2%. Among the topical OTC agents used to manage male AGA, minoxidil 5% applied twice daily was the most effective. Full article

(This article belongs to the Special Issue Pathophysiology of Hair Loss)

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16 pages, 11333 KiB

Open AccessArticle

Interferon-Linked Lipid and Bile Acid Imbalance Uncovered in Ankylosing Spondylitis in a Sibling-Controlled Multi-Omics Study

by Ze Wang, Yi Huang, Ziyu Guo, Jianhua Sun and Guoquan Zheng

Int. J. Mol. Sci. 2025, 26(16), 7919; https://doi.org/10.3390/ijms26167919 (registering DOI) - 16 Aug 2025

Abstract

Ankylosing spondylitis (AS) displays wide inter-patient variability that is not accounted for by HLA-B27 alone, suggesting that additional immune and metabolic modifiers contribute to disease severity. Using a genetically matched design, we profiled peripheral blood mononuclear cells from two brother pairs discordant for [...] Read more.

Ankylosing spondylitis (AS) displays wide inter-patient variability that is not accounted for by HLA-B27 alone, suggesting that additional immune and metabolic modifiers contribute to disease severity. Using a genetically matched design, we profiled peripheral blood mononuclear cells from two brother pairs discordant for AS severity and one healthy brother pair. Strand-specific RNA-seq was analyzed with a family-blocked DESeq2 model, while untargeted metabolites were quantified using gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS). Differential features were defined as follows: differentially expressed genes (DEGs) (|log₂FC| ≥ 1 and FDR < 0.05) and metabolites (VIP > 1, FC ≥ 1.2, and BH-adjusted p < 0.05). Pathway enrichment was performed with KEGG and Gene Ontology (GO). A total of 325 genes were differentially expressed. Type I interferon and neutrophil granule transcripts (e.g., IFI44L, ISG15, S100A8/A9) were markedly up-regulated, whereas mitochondrial β-oxidation genes (ACADM, CPT1A, ACOT12) were repressed. Metabolomics revealed 110 discriminant features, including 25 MS/MS-annotated metabolites. Primary bile acid intermediates were depleted, whereas oxidized fatty acid derivatives such as 12-Z-octadecadienal and palmitic amide accumulated. Spearman correlation identified two antagonistic modules (i) interferon/neutrophil genes linked to pro-oxidative lipids and (ii) lipid catabolism genes linked to bile acid species that persisted when severe and mild siblings were compared directly. Enrichment mapping associated these modules with viral defense, neutrophil degranulation, fatty acid β-oxidation, and bile acid biosynthesis pathways. This sibling-paired peripheral blood mononuclear cell (PBMC) dual-omics study delineates an interferon-driven lipid–bile acid axis that tracks AS severity, supporting composite PBMC-based biomarkers for future prospective validation and highlighting mitochondrial lipid clearance and bile acid homeostasis as potential therapeutic targets. Full article

(This article belongs to the Special Issue RNA Biology and Regulation)

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50 pages, 5154 KiB

Open AccessReview

Applications of Tailored Mesoporous Silicate Nanomaterials in Regenerative Medicine and Theranostics

by Jean Fotie

Int. J. Mol. Sci. 2025, 26(16), 7918; https://doi.org/10.3390/ijms26167918 (registering DOI) - 16 Aug 2025

Abstract

Tailored mesoporous silicate nanomaterials have attracted significant interest due to their exceptional surface properties, including high interfacial toughness, tunable thickness, customizable topology, optical transparency, and adjustable hydrophobicity. These characteristics enable them to exhibit a wide range of functional behaviors, such as antibacterial, anti-fouling, [...] Read more.

Tailored mesoporous silicate nanomaterials have attracted significant interest due to their exceptional surface properties, including high interfacial toughness, tunable thickness, customizable topology, optical transparency, and adjustable hydrophobicity. These characteristics enable them to exhibit a wide range of functional behaviors, such as antibacterial, anti-fouling, anti-fogging, lubricating, and abrasion-resistant properties, to name just a few. With recent advances in surface-modified nanosystems for bioengineering and biomedical applications, silica-based nanomaterials have emerged as promising candidates owing to their ease of surface functionalization, bioactivity, biocompatibility, biodegradability, and bioavailability. Consequently, they have been widely explored in various therapeutic contexts. This review provides a concise and concentrated summary of recent advances and applications of tailored mesoporous silicate nanomaterials in regenerative medicine and theranostics, with the primary focus being on how endogenous or exogenous triggers can be leveraged to achieve selective and precise delivery of various biomolecules and active therapeutics across diverse cellular environments, by harnessing the intrinsic properties of mesoporous silicate nanoparticles. This focus also guided the selection of specific examples provided to highlight their wide range of applications, with the report concluding with some perspectives and remaining challenges. Full article

(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in "Materials Science" Section)

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14 pages, 1306 KiB

Open AccessReview

Gold Nanoparticles as Targeted Drug Delivery Systems for Liver Cancer: A Systematic Review of Tumor Targeting Efficiency and Toxicity Profiles

by Meda Cosma, Teodora Mocan, Cristian Delcea, Teodora Pop, Ofelia Mosteanu and Lucian Mocan

Int. J. Mol. Sci. 2025, 26(16), 7917; https://doi.org/10.3390/ijms26167917 (registering DOI) - 16 Aug 2025

Abstract

Hepatocellular carcinoma (HC) ranks as the fifth most prevalent form of cancer among humans and is a significant contributor to cancer-related deaths. During the latest year, an interesting scientific fascination arose around gold nanoparticles (AUNPs) following the recovery of their remarkable properties. Some [...] Read more.

Hepatocellular carcinoma (HC) ranks as the fifth most prevalent form of cancer among humans and is a significant contributor to cancer-related deaths. During the latest year, an interesting scientific fascination arose around gold nanoparticles (AUNPs) following the recovery of their remarkable properties. Some studies suggest that AUNPs can enhance drug targeting in cancer treatment and reduce its toxicity. The major purpose of this paper is to systematically review the effectiveness, safety, and prospective mechanism of gold nanoparticles in delivering drugs for liver cancer treatment. Comprehensive research was conducted using major scientific databases (i.e., PubMed, Web of Science, and Scopus) to identify studies focusing on AUNPs in drug delivery systems. We mainly focused on studies that specifically analyzed liver cancer. The current results of the systematic review show that the application of gold nanoparticles (AUNPs) in liver cancer drug delivery enhances drug targeting to liver tumors. This efficient factor improves the bioavailability and elevates the therapeutic index of chemotherapeutic agents in treatment. This systematic review highlights the significant potential of AUNPs to increase the delivery of drugs for liver cancer treatment effectively. The major findings indicate that AUNPs improve the targeting and bioavailability of chemotherapeutic agents, enhancing therapeutic outcomes such as tumor suppression and improved survival rates. While the results of this review are encouraging; however, further research is necessary to ensure the safety and efficacy of AUNPs in clinical settings. Human trials must address concerns regarding long-term toxicity and regulatory approval. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies, 2nd Edition)

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4 pages, 181 KiB

Open AccessEditorial

Special Issue: “Advanced Research on Molecular Modeling of Protein Structure and Functions”

by Maria G. Khrenova

Int. J. Mol. Sci. 2025, 26(16), 7916; https://doi.org/10.3390/ijms26167916 (registering DOI) - 16 Aug 2025

Abstract

Recent developments in computer technologies, software and methods have made molecular modeling a powerful tool in experimental studies of biomolecular systems, and in their rational modification [...] Full article

(This article belongs to the Special Issue Advanced Research in Molecular Modeling of Protein Structure and Functions)

16 pages, 1008 KiB

Open AccessReview

Fusobacterium nucleatum and Gastric Cancer: An Emerging Connection

by Joana Sorino, Mario Della Mura, Giuseppe Ingravallo, Gerardo Cazzato, Cristina Pizzimenti, Valeria Zuccalà, Ludovica Pepe, Emanuela Germanà, Maurizio Martini, Antonio Ieni and Vincenzo Fiorentino

Int. J. Mol. Sci. 2025, 26(16), 7915; https://doi.org/10.3390/ijms26167915 (registering DOI) - 16 Aug 2025

Abstract

Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe traditionally associated with periodontal disease, has recently emerged as a putative contributor to gastric carcinoma (GC) pathogenesis. Beyond its detection in gastric tissues, particularly in patients negative for Helicobacter pylori (H. pylori) [...] Read more.

Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe traditionally associated with periodontal disease, has recently emerged as a putative contributor to gastric carcinoma (GC) pathogenesis. Beyond its detection in gastric tissues, particularly in patients negative for Helicobacter pylori (H. pylori) or in advanced GC cases, F. nucleatum exerts diverse oncogenic effects. It promotes GC progression by modulating the tumor microenvironment through IL−17/NF-κB signaling, inducing tumor-associated neutrophils (TANs), upregulating PD-L1 expression, and enhancing immune evasion. Moreover, it increases tumor invasiveness via cytoskeletal reorganization, while extracellular vesicles (EVs) induced by the infection contribute to tumor cell proliferation, invasion, and migration. Clinically, its presence correlates with increased tumor mutational burden (TMB), venous thromboembolism, and poor prognosis. This review summarizes the current evidence regarding the emerging role of F. nucleatum in gastric tumorigenesis, examines its potential utility as a diagnostic and prognostic biomarker within the framework of precision oncology, and outlines the molecular methodologies presently employed for its detection in gastric tissue specimens. Full article

(This article belongs to the Collection Latest Review Papers in Molecular Microbiology)

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