Experimental Biology And Medicine (Maywood, N.J.)[JOURNAL]
Sun
200 papers
Global MyoG research 2004-2024: a bibliometric analysis of trends and translational implications.
Hu L, Zhuang W, Chen W … +5 more , Yang S, Chen S, Wang X, Gao Q, Chen J
Exp Biol Med (Maywood) · 2026 · PMID 41868599 · Full text
Myogenin (MyoG) is a core myogenic transcription factor that orchestrates myoblast differentiation and myofiber maturation and has been increasingly implicated in skeletal muscle degeneration and rhabdomyosarcoma, yet it...
Myogenin (MyoG) is a core myogenic transcription factor that orchestrates myoblast differentiation and myofiber maturation and has been increasingly implicated in skeletal muscle degeneration and rhabdomyosarcoma, yet its global research landscape has not been systematically characterized. In this study, we performed a bibliometric analysis of MyoG-related publications from 2004 to 2024 retrieved from the Web of Science Core Collection. A total of 402 articles authored by 2,402 researchers from 1,148 institutions across 165 countries and regions were analyzed using VOSviewer, CiteSpace and R-based bibliometric tools. We quantified annual publication output, identified leading countries, institutions, authors and journals, and reconstructed collaboration, co-citation and keyword co-occurrence networks to delineate thematic evolution. The global pattern showed a multipolar structure dominated by the United States and China, with European institutions forming an additional hub and emerging countries contributing with growing but comparatively lower impact. Research hotspots exhibited a clear progression from early work on molecular mechanisms (DNA binding, MyoD family interactions, chromatin remodelling) toward regenerative biology (satellite cell regulation, muscle regeneration) and, more recently, disease-oriented studies focused on muscle atrophy, Duchenne muscular dystrophy and rhabdomyosarcoma. Landmark co-cited studies established MyoG as an indispensable regulator of skeletal muscle differentiation and highlighted its expanding relevance in pathological remodelling and therapeutic targeting. Future work is expected to concentrate on decoding MyoG-centred regulatory networks in degenerative muscle disease, integrating single-cell and spatial transcriptomics with functional genomics and multi-omics, and developing MyoG-based diagnostic and targeted therapeutic strategies. Despite the intrinsic limitations of single-database and citation-based approaches, this study provides a panoramic overview of two decades of MyoG research and offers a structured framework to guide future basic and translational investigations in muscle biology and oncology.
A novel variant causes autosomal dominant intellectual developmental disorder 66 by disrupting calcium homeostasis via impaired membrane trafficking.
Zang H, Yang X, Liu Y … +2 more , Ma C, Yang D
Exp Biol Med (Maywood) · 2026 · PMID 41853798 · Full text
Heterozygous pathogenic variants in (encoding PMCA1) cause autosomal dominant intellectual developmental disorder 66 (MRD66; OMIM #619910). To date, only 12 pathogenic variants have been reported in MRD66. This study a...
Heterozygous pathogenic variants in (encoding PMCA1) cause autosomal dominant intellectual developmental disorder 66 (MRD66; OMIM #619910). To date, only 12 pathogenic variants have been reported in MRD66. This study aimed to identify the genetic etiology in a Chinese infant with a neurodevelopmental disorder characterized by early-onset seizures and global developmental delay (GDD) and functionally characterize a novel missense variant. Trio-based whole-exome sequencing revealed a heterozygous variant (c.2140A>C, p.Thr714Pro) in the proband. The proband presented with infantile spasms, GDD (Gesell Developmental Quotient: 65-74), and severe growth restriction (height/weight <-2 SD). To investigate the variant's pathogenicity, the wild-type (WT) and mutant constructs, N-terminally tagged with mScarlet, were transfected into HEK293T cells. Confocal imaging demonstrated profound cytoplasmic mislocalization of the p.Thr714Pro mutant protein, contrasting sharply with the characteristic plasma membrane localization of WT ATP2B1. Measurement of intracellular Ca levels using Fluo-4 AM showed a significant 2.07-fold increase in basal Ca levels in cells expressing the mutant compared to WT. This finding expands the spectrum of ATP2B1 variants associated with MRD66 and confirms calcium dyshomeostasis as the core pathomechanism. This case of MRD66 demonstrates a very early onset of seizures, consistent with the recognized phenotypic variability and the critical role of PMCA1 in early neurodevelopment.
Ananalysis of the effects of Treg cell therapy intervention on the gut microbiota of type 1 diabetic mice using 16S rRNA gene sequencing.
Zhou M, Du K, Wang H … +6 more , Zhang Z, Zhao R, Ma C, Huang Q, Zhang W, Chen W
Exp Biol Med (Maywood) · 2026 · PMID 41853797 · Full text
This study established a type 1 diabetes (T1DM) mouse model via intraperitoneal injection of streptozotocin (STZ) and examined the effect of regulatory T (Treg) cells on the gut microbiota by comparing its composition an...
This study established a type 1 diabetes (T1DM) mouse model via intraperitoneal injection of streptozotocin (STZ) and examined the effect of regulatory T (Treg) cells on the gut microbiota by comparing its composition and diversity across three groups: control, T1DM, and Treg-treated mice. Forty-one 8-week-old male C57BL/6 mice under specific pathogen-free conditions were divided into a healthy control group, an untreated T1DM group, and a Treg treatment group (receiving low, medium, or high doses). T1DM was induced by administering a low-dose STZ injection over five consecutive days, with diabetes confirmation defined as a blood glucose level ≥300 mg/dL. CD4+CD25+ Treg cells isolated from spleens of healthy mice were used for treatment. Fecal samples collected on days 0, 14, and 34 from three randomly selected mice per group were subjected to 16S rRNA gene sequencing targeting the V3-V4 regions. The results showed significant differences in both alpha and beta diversity among the groups. Dominant bacterial families varied: Ruminococcaceae and others were enriched in the Treg treatment group, Muribaculaceae in the control group, and Lactobacillaceae in the untreated T1DM group. Genus-level abundances also shifted over time. Firmicutes abundance positively correlated with Treg levels (r = 0.70, p = 0.0433) but negatively with IFN-γ, whereas Cyanobacteria exhibited the opposite correlation. The Firmicutes/Bacteroidetes ratio was higher in T1DM mice than in controls and lower in the Treg-treated group. Metabolic pathway analysis indicated that two-component systems and ABC transporters were more prevalent in T1DM mice. In summary, Treg cell treatment altered the diversity, composition, dominant taxa, and Firmicutes/Bacteroidetes ratio of the gut microbiota compared with untreated T1DM mice.
Skeletal muscle reprogramming in peripheral nerve injury: mechanisms, therapeutic roles, and complication management.
Long F, Pan X, He A … +3 more , Wang X, Wei Z, Gao S
Exp Biol Med (Maywood) · 2026 · PMID 41847509 · Full text
Peripheral nerve injury (PNI) presents a significant clinical challenge, frequently leading to long-term neuromuscular dysfunction, muscle atrophy, fibrosis, and chronic pain. Traditional repair strategies, including mic...
Peripheral nerve injury (PNI) presents a significant clinical challenge, frequently leading to long-term neuromuscular dysfunction, muscle atrophy, fibrosis, and chronic pain. Traditional repair strategies, including microsurgical reconnection and neurotrophic support, often yield limited functional recovery, especially in cases of delayed or incomplete reinnervation. In this context, skeletal muscle reprogramming-defined as the intentional modulation of cellular fate, function, or metabolic state in muscle-resident cells-has emerged as a promising strategy to enhance regenerative outcomes. This process involves transcriptional, epigenetic, and metabolic interventions targeting myogenic progenitors, fibro-adipogenic progenitors (FAPs), satellite cells (MuSCs), and the broader muscle microenvironment. Recent studies demonstrate that reprogramming strategies can mitigate denervation-induced muscle atrophy, delay fibrotic remodeling, promote neuromuscular junction (NMJ) reconstruction, and even stimulate endogenous nerve regrowth via retrograde signaling. Mechanistic insights have uncovered pivotal roles for signaling pathways such as Wnt/β-catenin, TGF-β, Notch, and HDAC-regulated chromatin dynamics. Furthermore, innovations in small molecule cocktails, CRISPR-based transcriptional reactivation, and metabolic rewiring have expanded the therapeutic toolkit for muscle preservation and regeneration. This review comprehensively examines the molecular mechanisms, therapeutic roles, and translational challenges of skeletal muscle reprogramming in the context of PNI. We explore how muscle-targeted interventions can address complications of denervation, improve the efficacy of nerve repair, and offer a synergistic axis of regeneration when integrated with nerve-centric strategies. Finally, we identify key knowledge gaps and outline future research directions required to translate reprogramming-based therapies into clinical practice.
Identification of potential hub genes related to ferroptosis and hypoxia in dilated cardiomyopathy: a bioinformatic analysis with preliminary experimental validation.
Wang X, Ginting CN, Leslie W
Exp Biol Med (Maywood) · 2026 · PMID 41847508 · Full text
The study aims to explore the potential role of ferroptosis and hypoxia in dilated cardiomyopathy (DCM). GSE120895, GSE17800, GSE112556, ferroptosis-related genes (FRGs), and hypoxia-related genes (HRGs) were downloaded...
The study aims to explore the potential role of ferroptosis and hypoxia in dilated cardiomyopathy (DCM). GSE120895, GSE17800, GSE112556, ferroptosis-related genes (FRGs), and hypoxia-related genes (HRGs) were downloaded from the public dataset. Ferroptosis- and hypoxia-related differentially expressed genes (DEGs) and DCM-related genes were obtained. Subsequentially, hub genes were identified, and their diagnostic values were assessed. Next, immune cell infiltration analysis, drug prediction and molecular docking were carried out based on the hub genes. Finally, the hub gene TGM2 was preliminarily verified . A total of 18 ferroptosis- and hypoxia-related DEGs and 315 DCM-related genes were acquired. Subsequently, 6 hub genes (PPP1R15A, TGM2, MAP3K5, USP7, SESN2, and ADAM23) were obtained and have potential diagnostic value. Immune infiltration analysis showed that CD56dim natural killer (NK) cells, macrophages, monocytes, NK cells, and NK T cells were significantly infiltrated in DCM patients. Furthermore, the lncRNA-miRNA-mRNA network was constructed. Moreover, 16 drugs were predicted, and the binding energy between atorvastatin and TGM2 was -2.79 kcal/mol. verification showed that TGM2, PPP1R15A and SESN2 were up-regulated in DOX-induced AC16 cardiomyocyte injury. After knocking down TGM2, the expressions of α-actinin and cTnT were increased, and the expression level of HIF-1α was inhibited. Dual luciferase assay showed that hsa-miR-291-5p exerted its regulatory effect by directly binding to TGM2. Flow cytometry results showed that TGM2 had no significant effect on the apoptosis of AC16 cells. Our findings may provide new ideas for the diagnosis and treatment of DCM.
L-Glutamine attenuates peritoneal fibrosis developed in 5-Fluorouracil-treated mice.
Heleno JFG, Dos Santos LCC, Fontes IC … +8 more , Paiva Silva MRA, Correia LB, Silva NDG, Prazeres PHDM, Goulart Guimarães PP, Gilroy DW, Andrade SP, Campos PP
Exp Biol Med (Maywood) · 2026 · PMID 41815822 · Full text
Peritoneal fibrosis is an adverse effect of cancer therapy leading to progressive organ failure. L-Glutamine supplementation has been shown to attenuate fibrosis and improve wound healing in several types of tissue injur...
Peritoneal fibrosis is an adverse effect of cancer therapy leading to progressive organ failure. L-Glutamine supplementation has been shown to attenuate fibrosis and improve wound healing in several types of tissue injuries. The aim of this study was to evaluate the effects of this supplementation on key components of the peritoneal fibrovascular tissue induced by implants in mice treated with 5-Fluorouracil (5-FU) C57BL/6 mice received three intraperitoneal doses of immunosuppressant (60, 40, and 40 mg/kg) on non-consecutive days prior to implantation of polyether-polyurethane sponges into the peritoneal cavity. The group treated with L-Glutamine received 150 mg/kg/day for 7 days (oral gavage) starting 24 h after implantation and the control group received filtered water. Eight days after implantation, implants were removed and processed for inflammatory, angiogenic, and fibrogenic markers. Flow cytometry results showed that L-Glutamine decreased (48%) the frequency/influx of total intra-implant cells. The remaining cell population in the treated group had more neutrophils, lymphocytes, and macrophages than in the control. Immunohistochemistry analysis showed fewer Caspase-3-positive cells in the treated group. Myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities, TNF-α levels, and mast cell numbers were decreased in the implants of the L-Glutamine-treated group compared with the control. Similarly, angiogenesis (VEGF levels and number of blood vessels) was attenuated by L-Glutamine. Supplementation also decreased the amount of intra-implant collagen and TGF-β1 levels. These results indicate that L-Glutamine attenuates critical inflammatory-angiogenesis and profibrotic pathways involved in fibrosis development in immunosuppression conditions, supporting its potential as an adjunct therapeutic strategy for managing peritoneal healing in cancer.
Intra- and extrapulmonary lipopolysaccharides-induced acute lung injury and pharmacotherapeutic response patterns in ventilated 7-day-old rabbits.
Zhuang G, Gu Q, Xie S … +2 more , Guo X, Sun B
Exp Biol Med (Maywood) · 2026 · PMID 41815821 · Full text
We explored pharmacotherapeutic response patterns of lipopolysaccharides (LPS)-induced pneumonia and sepsis as direct and indirect acute lung injury (ALI), and efficacy of a combined surfactant (S) and inhaled nitric oxi...
We explored pharmacotherapeutic response patterns of lipopolysaccharides (LPS)-induced pneumonia and sepsis as direct and indirect acute lung injury (ALI), and efficacy of a combined surfactant (S) and inhaled nitric oxide (iNO), simulating critical care, in rabbits of post-neonatal infancy. Anaesthetized 7-day-old healthy rabbits were injected intratracheally (IT) or intravenously (IV) with LPS (15-20-25 mg/kg, L) or saline as a control (C), and subjected to initial 2-hour mechanical ventilation (MV) with standardized tidal volume to induce ALI. They were then treated with S (200 mg/kg) and iNO (10 ppm, N), or not, thereby allocating to 6 groups (ITC, ITL, ITLSN, IVC, IVL, IVLSN) for another 8 h. Survival time/rate (ST), and variables as biomarkers in lung physiology, histopathology, biochemistry, and pathophysiology were measured. The survival was LPS-route, but not dosing, dependent. Compared to the IVL, ITL had relatively higher ST, lung injury score (LIS), lower intrapulmonary phospholipid pools, mRNA expressions in surfactant proteins (SPs) and pulmonary vascular endothelial cell injury (VEI)-related variables. ITLSN had higher phospholipid pools but no improvement in ST, lung mechanics, LIS or mRNA expression of SPs, proinflammatory mediators and VEI-related variables. IVLSN had improved lung mechanics, LIS, phospholipid pools, and SP-A mRNA expression, but worse ST, metabolic acidosis, higher interleukin mRNA expression in the lungs, liver and kidney, suspected as sepsis-associated multiorgan involvement. Using the infant rabbit LPS-ALI model, we characterized the survival as LPS-route dependent, the lung impairment and response pattern in surfactant and iNO treatment ineffectiveness/failure, as pharmacotherapeutic response patterns, with causal implication pertinent to the underlying pathophysiology of experimental pediatric ARDS.
The effect of short-term consumption of on the gut microbiome of obese individuals.
Burakova I, Smirnova Y, Morozova P … +5 more , Pogorelova S, Kryukova O, Kislova T, Korneeva O, Syromyatnikov M
Exp Biol Med (Maywood) · 2026 · PMID 41809656 · Full text
It is known that gut microbiota dysbiosis can lead to obesity by disrupting energy consumption and metabolism. Probiotic supplements are a potential therapeutic option for improving intestinal homeostasis. The aim of thi...
It is known that gut microbiota dysbiosis can lead to obesity by disrupting energy consumption and metabolism. Probiotic supplements are a potential therapeutic option for improving intestinal homeostasis. The aim of this study was to investigate the effect of a probiotic supplement containing on the intestinal microbiome of people with obesity using high-throughput sequencing on the DNBSEQ-G50 platform. The study demonstrated a positive effect of the supplement on bacterial species such as , , , , and . Therefore, we suggest the potential use of this bacterial species in the treatment of gut microbiota dysbiosis of obese individuals.
The gut-retina axis in age-related macular degeneration: immune crosstalk and metabolite production.
Zhou B, Parekh Z, Phung C … +2 more , Rodriguez SH, Skondra D
Exp Biol Med (Maywood) · 2026 · PMID 41809655 · Full text
Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbio...
Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbiome as a potential critical modulator in AMD pathogenesis through the gut-retina axis. Dysbiosis, characterized by imbalanced microbial diversity, composition and function, can exacerbate systemic and retinal inflammation through microglial priming, inflammasome activation, and secretion of pro-angiogenic cytokines (IL-6, IL-1β, TNF-α, VEGF). Additionally, microbiome-derived metabolites such as short-chain fatty acids and bile acids may exert modulatory roles in host immunity and homeostasis. Their depletion in conjunction with enrichment of specific microbial taxa have been linked to progression of advanced AMD. Together, these complex systems of immune crosstalk in relation to dysbiosis highlight the gut-retina axis as a promising therapeutic target. Dietary modifications, particularly Mediterranean and high-fiber diets, enhance production of protective metabolites and are associated with decreased AMD progression risk compared to Western dietary patterns. Experimental strategies such as fecal microbiota transplantation in animal models and drug repurposing strategies show promise in modulating disease severity. This review synthesizes current mechanistic insights into microbial-immune crosstalk in AMD, emphasizing the interplay of dysbiosis, immune activation, and metabolite signaling.
Poliovirus receptor (PVR) expression as a predictor of relapse in colorectal cancer: bioinformatics and virtual screening.
Alhudaithi SS, Salih MHR, AlHusseini ZH … +9 more , Almufadhili SM, Alelayani N, Bakheit AH, Alkahtani HM, Asiri HH, Alshamrani AA, Alhoshani AR, Alotaibi MR, As Sobeai HM
Exp Biol Med (Maywood) · 2026 · PMID 41767749 · Full text
Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. Despite advancements in CRC treatment strategies in recent years, disease recurrence remains a major problem; relapsed patients have...
Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. Despite advancements in CRC treatment strategies in recent years, disease recurrence remains a major problem; relapsed patients have a poorer prognosis and higher mortality risk. Several factors have been associated with CRC relapse. However, the role of immune checkpoints in CRC recurrence remains elusive. In this work, we aimed to investigate immune checkpoint genes correlated with recurrence in CRC, evaluate their potential as prognostic biomarkers, and identify promising immune checkpoint inhibitors through molecular docking and molecular dynamics simulations. Clinical, genetic, and epigenetic data of relapsed and relapse-free CRC patients in the Cancer Genome Atlas were retrieved from the cBioportal database and evaluated. Subsequently, molecular docking and molecular dynamics simulations studies were conducted to identify suitable poliovirus receptor ()/TIGIT binders. is a ligand for TIGIT and competes with CD226. The crystal structure used for docking was obtained from the Protein Data Bank (PDB ID: 3UDW). Using this investigative approach, clinical parameters data revealed that among immune checkpoint genes, the gene was significantly upregulated in relapsed patients. That upregulation was strongly correlated with diagnosis age, Aneuploidy, fraction genome alterations, and mutation count. Furthermore, free survival analysis showed that patients exhibiting elevated levels were 2.16 times more likely to relapse than those with low expression ( = 0.039). Virtual screening identified 106 natural compounds as potential binders at the /TIGIT interface. Molecular docking and molecular dynamics simulations identified three binders that exhibit favorable interactions with , with ZINC001848443492 emerging as the most promising. The results underscore the potential role of as a prognostic biomarker for relapse in CRC. Future studies, including TIGIT-PVR blockade assays and assessments of the impact of predicted PVR/TIGIT interface binders on T cell function, are necessary to validate this study's findings.
How can we balance risk and benefit of interleukin-18 armored T cell therapies?
Vicenova P, Maher J
Exp Biol Med (Maywood) · 2026 · PMID 41728085 · Full text
CD19-specific CAR T cells engineered to secrete a constitutively active form of the pro-inflammatory cytokine, interleukin (IL)-18 have demonstrated impressive efficacy in a recent clinical trial involving subjects who h...
CD19-specific CAR T cells engineered to secrete a constitutively active form of the pro-inflammatory cytokine, interleukin (IL)-18 have demonstrated impressive efficacy in a recent clinical trial involving subjects who had failed prior CAR T cell therapy. Corroborating these clinical data, preclinical studies of IL-18-armored CAR and T cell receptor-engineered T cells have demonstrated enhanced anti-tumor activity in several xenograft and syngeneic mouse cancer models. Interleukin-18 improves tumor clearance via direct effects on CAR T cells and indirect actions on cells on a variety of host immune cells, including natural killer, macrophage and dendritic cells. Compared to unarmored CAR T cells, IL-18-secreting CAR T cells are less exhausted, expand more efficiently and produce greater quantities of interferon (IFN)-γ. However, upregulated circulating IL-18 and its downstream mediator, IFN-γ, are also associated with systemic toxicities which have proven to be severe on occasions. In light of this, several groups have developed strategies that set out to restrict IL-18 release or biological activity to the tumor microenvironment. Among these, CAR T cells armored with NFAT-inducible IL-18 are now undergoing clinical testing. The evaluation of inducible or tumor-selective IL-18 deployment will show whether it is possible to minimize IL-18 related systemic toxicities while preserving localized amplification of anti-tumor activity.
Electrotherapy in the management of neuropathic corneal pain: narrative review.
Shanmathi AV, Yu M, Liu C … +3 more , Lee IXY, Tong L, Liu YC
Exp Biol Med (Maywood) · 2026 · PMID 41728084 · Full text
Neuropathic corneal pain (NCP) is a debilitating condition resulting from corneal nerve damage or dysfunction, leading to persistent ocular pain, discomfort and hypersensitivity. Conventional therapy with eye drops often...
Neuropathic corneal pain (NCP) is a debilitating condition resulting from corneal nerve damage or dysfunction, leading to persistent ocular pain, discomfort and hypersensitivity. Conventional therapy with eye drops often provides inadequate relief, necessitating the need for alternative therapeutic approaches. This review explores the role of electrotherapy in managing NCP, including its mechanisms, clinical efficacy, and potential integration into multimodal treatment strategies. We examine current evidence on various electrotherapy modalities such as transcutaneous electrical nerve stimulation, neurostimulation, and microcurrent stimulation. These electrotherapies have the potential to modulate pain pathways, promote nerve regeneration, and restore corneal homeostasis. Emerging studies suggest electrotherapy may alleviate NCP by altering neural signaling and reducing hyperalgesia. Integrating electrotherapy into existing pain management strategies may enhance the outcomes for patients with refractory NCP. However, its clinical application remains limited by a lack of standardized protocols and robust clinical trials. Although electrotherapy presents a promising and non-invasive option for NCP management, further research is needed to optimize the treatment parameters and optimal duration, assess the long-term efficacy, and establish guidelines for clinical use.
Expanding the clinical and genetic spectrum of -associated retinitis pigmentosa.
Amaral RAS, Zin OA, Resende RG … +5 more , Moraes DN, Salles MV, Rodrigues GD, Motta FL, Sallum JMF
Exp Biol Med (Maywood) · 2026 · PMID 41716464 · Full text
The majority of cases of autosomal-dominant retinitis pigmentosa (adRP) are associated with rhodopsin variants. More than 290 pathogenic variants responsible for 25%-30% of adRP cases have been identified to date. This...
The majority of cases of autosomal-dominant retinitis pigmentosa (adRP) are associated with rhodopsin variants. More than 290 pathogenic variants responsible for 25%-30% of adRP cases have been identified to date. This retrospective report focuses on and RP cases in the Brazilian population. Patients with molecular confirmation of pathogenic variants in the gene were included. Their clinical and genetic data were analyzed. Segregation analyses were included where possible. Cases were classified as generalized RP or sector RP according to fundus examinations and imaging data. The medical records of 43 patients from 34 families with -associated RP were reviewed. Twenty-two disease-causing variants of the and four previously unreported variants (c.317G>T; c.937-2A>T, c.272_283del, and c.530+1G>C) were identified. The majority of cases involved missense variants. The most prevalent variant was c.551A>G, p.(Gln184Arg), which was identified in seven patients (21%) from four families. One patient presented with the splice donor variant c.530+1G>C in the homozygous state, which was classified as pathogenic. Thirty-two patients presented with a generalized RP phenotype, and six patients were diagnosed with sector RP. This study provides information on the clinical and genetic features of -associated RP in the Brazilian population, expanding the spectrum of gene disease-causing variant frequencies.
Expression of MicroRNA-155 and its associations with EBV serological markers and inflammatory cytokines in young lymphoma patients with evidence of active EBV infection.
Mohammed LM, Ali PS, Taha AQ … +1 more , Mohammad LM
Exp Biol Med (Maywood) · 2026 · PMID 41709959 · Full text
The Epstein-Barr virus (EBV) is implicated in several lymphoproliferative disorders, particularly among children and adolescents who frequently experience primary EBV infection. MicroRNA-155 (miR-155), an oncogenic and i...
The Epstein-Barr virus (EBV) is implicated in several lymphoproliferative disorders, particularly among children and adolescents who frequently experience primary EBV infection. MicroRNA-155 (miR-155), an oncogenic and immunoregulatory molecule, is known to participate in EBV-related immune modulation; however, its expression profile and relationship with EBV serological markers and inflammatory cytokines in young lymphoma patients remain insufficiently characterized. This cross-sectional observational study included 80 participants, comprising 40 young lymphoma patients with serological evidence of active EBV infection and 40 healthy controls. Serum EBV IgM and IgG levels were measured using ELISA, as were IL-18 and IL-32 concentrations, while serum miR-155 levels were quantified using qRT-PCR with an absolute quantification approach. The mean age of participants was 13.19 ± 2.51 years, and 55% were male. Serum miR-155 levels were significantly higher in lymphoma patients compared with controls (median: 1.13 vs. 0.43 ng/mL; p = 0.012). Elevated miR-155 expression was significantly associated with EBV IgM positivity (p < 0.001), IL-18 (p = 0.001), and IL-32 (p < 0.001). In multivariate logistic regression analysis, IL-32 positivity emerged as a strong independent predictor of elevated miR-155 levels (AOR = 19.02, p = 0.001). Receiver operating characteristic curve analysis demonstrated good discriminative performance of miR-155 (AUC = 0.87), with 87% sensitivity and 90% specificity at a cutoff value of ≥1.11 ng/mL. These findings indicate that serum miR-155 is significantly elevated in young lymphoma patients with serological evidence of active EBV infection and is statistically associated with inflammatory cytokines, particularly IL-32. miR-155 may represent a promising non-invasive biomarker reflecting EBV-related immune activation, although tissue-based EBV confirmation and mechanistic studies are required to establish causality.
Integrated tear proteomics define the molecular blueprint of corneal epithelial repair.
Feret N, Decoudu M, Vialaret J … +4 more , Hirtz C, Loulier K, Daien V, Michon F
Exp Biol Med (Maywood) · 2025 · PMID 41704577 · Full text
Tears are easy to collect, repeatable, and reflect the state of the corneal surface-attributes that make them attractive for bedside monitoring after surgery or injury. We performed a cross-species meta-analysis of tear...
Tears are easy to collect, repeatable, and reflect the state of the corneal surface-attributes that make them attractive for bedside monitoring after surgery or injury. We performed a cross-species meta-analysis of tear proteomes from patients undergoing photorefractive keratectomy (PRK) and from mice after mechanical epithelial abrasion to define molecular programs that are both conserved and clinically actionable. Roughly one-third of the injury response was shared between species, centering on innate immune activation (complement/acute phase), epithelial migration and cytoskeletal remodeling, and a calibrated suppression of proteolysis. From this overlap we distilled a small, secreted tear panel that stages injury and early resolution in both species: transferrin and hemopexin (iron/heme scavenging), albumin (vascular leak), apolipoprotein A-I (barrier lipid transport), and the coagulation modulators kininogen-1 and α2-antiplasmin (protease/fibrinolysis control). This panel rises at the first post-injury sampling (D0 in humans; 6-12 h in mice) and trends toward baseline during recovery (D3 in humans; ∼24 h in mice), providing a practical kinetic signature for clinical decision-making. Standardized sampling at D0/D3 can therefore quantify acute damage and early healing, enable pharmacodynamic readouts for anti-inflammatory or barrier-stabilizing therapies, and support risk stratification after epithelial procedures. Species-specific differences (human: secretory/immune surveillance; mouse: mitochondrial/metabolic reboot) clarify which preclinical signals are most likely to translate. Together, these findings establish a conserved tear blueprint of corneal repair and nominate a minimal, deployable biomarker set to accelerate clinical monitoring and therapeutic development in ocular surface disease.
Causal effects of antibody-mediated immunity to pathogens on five ophthalmic diseases: a Mendelian randomization study.
Pan L, Deng J, Yang J … +4 more , Wang M, Chen Z, Wang T, Li Y
Exp Biol Med (Maywood) · 2026 · PMID 41694267 · Full text
While immune responses related to infections have been linked to ocular diseases, their causal role remains to be established. This study aimed to assess the causal relationship between antibody-mediated immune responses...
While immune responses related to infections have been linked to ocular diseases, their causal role remains to be established. This study aimed to assess the causal relationship between antibody-mediated immune responses to infectious agents and five ocular conditions: chronic iridocyclitis (CIR), scleritis, wet age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. We performed a two-sample Mendelian randomization (MR) analysis using GWAS data to assess causality between antibody responses to 46 pathogens and five ophthalmic diseases. The instrumental variables were Single nucleotide polymorphisms (SNPs). Causal estimates were primarily generated via the inverse-variance weighted method, supplemented by MR-Egger and weighted median methods. A Bonferroni-corrected threshold of P < 2.17 × 10 was applied. Sensitivity analyses included Cochran's Q, MR-Egger, and MR-PRESSO for heterogeneity and pleiotropy. Reverse MR was performed to assess bidirectionality. Forward MR identified causal effects of infection-induced immune responses on ocular diseases. Epstein-Barr virus (EBV) ZEBRA antibodies were positively correlated with CIR, whereas Varicella zoster virus glycoproteins E and I antibodies were associated with scleritis and DR as risk factors. Genetically predicted anti-polyomavirus 2 IgG seropositivity (JCV IgG+) was identified as a risk factor for DR, wet AMD and glaucoma. In contrast, The EBV EBNA-1 antibody is associated with DR, wet AMD, and glaucoma as a protective factor, whereas the EBV VCA18 antibody is negatively associated with wet AMD. Reverse MR analysis indicated that DR may elevate JCV VP1 antibody levels. This study provides the first genetic evidence of a causal link between pathogen-specific immune responses and ocular diseases, offering a foundation for targeted immunomodulatory and personalized therapies.
Maternal diet-induced hypercholanemia alters gut microbiota and metabolome in adult female Western diet-fed offspring.
Ovadia C, McIlvride S, Schoonejans JM … +9 more , Spagou K, Gómez-Romero M, Smith A, Papacleovoulou G, Nikolova V, Dixon PH, Holmes E, Marchesi JR, Williamson C
Exp Biol Med (Maywood) · 2026 · PMID 41694266 · Full text
Children of mothers with intrahepatic cholestasis of pregnancy (ICP) are more likely to develop metabolic disease later in life. Using a mouse model of gestational cholestasis, we previously found that 18-week-old offspr...
Children of mothers with intrahepatic cholestasis of pregnancy (ICP) are more likely to develop metabolic disease later in life. Using a mouse model of gestational cholestasis, we previously found that 18-week-old offspring had metabolic alterations that were exacerbated in female offspring when challenged with a Western diet (WD). Microbiota changes are emerging as a potential mechanism for developmental programming, and the maternal gut microbiota is known to be altered in pregnancy and in ICP. We hypothesized that, in our model, the offspring gut microbiota is altered by maternal gestational disease, potentially impacting future offspring metabolic health. Female mice were fed a cholic acid (CA)-supplemented diet for 1 week preceding and throughout pregnancy to mimic gestational hypercholanemia. Female offspring were challenged with a WD from 12 to 18 weeks of age and cecal contents were collected for metataxonomics and metabolomic profiling. Maternal CA dietary supplementation was associated with markedly increased cecal sulfated bile acid species (up to 387-fold increase). Whilst WD-feeding of offspring was associated with a greater proportion of primary to secondary bile acids, and more tauro-conjugated bile acids than for offspring fed a normal diet, this adaptation to WD-feeding was not evident for those whose mothers were fed a CA-supplemented diet. Indeed, WD-fed offspring of CA-supplemented mothers had a >2-fold reduction in CA and dehydrocholic acid levels compared to those from NC-fed mothers. This corresponded with an altered profile of cecal microbiota, with clear separation of microbiotal profiles according to maternal diet in the WD-fed, but not NC-fed, offspring. This observational mouse study has shown that exposure to maternal hypercholanemia can significantly impact the effects of an obesogenic diet on offspring intestinal bile acid metabolism and gut microbiota, likely increasing their vulnerability to metabolic dysfunction when exposed to the "second hit" of an unhealthy postnatal environment.
Pulmonary injury following exposure to amorphous silicon dioxide nanoparticles in .
Renda RP, Cerreta JM
Exp Biol Med (Maywood) · 2026 · PMID 41669491 · Full text
Amorphous silicon dioxide nanoparticles (SiO NPs) are abundant within the earth's crust and can be released into the air through industrial and manufacturing activities. Such materials are often used in industrial proces...
Amorphous silicon dioxide nanoparticles (SiO NPs) are abundant within the earth's crust and can be released into the air through industrial and manufacturing activities. Such materials are often used in industrial processes, in pharmaceutical and in the cosmetic industries. Amorphous SiO NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity of SiO NPs was assessed using inhalation exposure in an system to study a possible mechanism of pulmonary injury. Golden Syrian Hamsters were divided into 4 groups: 1- room air control, 2- vehicle control, 3- low concentration (6 mg/m) and 4- high concentration (12 mg/m). Hamsters were treated for 4 h a day for 8 days. Bronchoalveolar Lavage Fluid (BALF) analysis found increases in total cell counts (p < 0.0001), neutrophils (p < 0.0001), lymphocytes (p < 0.001), eosinophils (p < 0.01), multinucleated macrophages (p < 0.01), total protein (p < 0.0001), alkaline phosphatase (p < 0.0001), and lactate dehydrogenase (p < 0.001) in the high concentration group. Histopathological analysis found an increase in air space, quantified by Mean Linear Intercept (p < 0.0001), and a significant increase in TUNEL positive cells (p < 0.001), in the high concentration group. SEM and TEM found structural alterations to the lung tissue including increase in the number holes in the alveolar walls and in apoptotic bodies within tissue. Caspase 3 (p < 0.05), and 8 (p < 0.05), were significantly increased along with cellular inflammation markers TNF-α (p < 0.05), and HSP70 (p < 0.05) in the high concentration group. Results of the study indicate exposure to SiO NPs may induce extrinsic apoptotic pathway, leading to tissue damage and significant airspace enlargement.
Role of NAD metabolism-related genes in diabetic nephropathy: subtype classification, biomarker identification, and association with renal function.
Zeng S, Tao Y, Guo H
Exp Biol Med (Maywood) · 2025 · PMID 41669232 · Full text
Diabetic nephropathy (DN) remains a major complication of diabetes, significantly impacting renal function. Emerging evidence suggests that NAD metabolism plays a crucial role in DN pathogenesis. This study investigates...
Diabetic nephropathy (DN) remains a major complication of diabetes, significantly impacting renal function. Emerging evidence suggests that NAD metabolism plays a crucial role in DN pathogenesis. This study investigates the roles of NAD metabolism-related genes in DN and how there are associated with different disease subtypes. We analyzed gene expression data from DN-associated datasets (GSE30528 and GSE30529) to identify differences in NAD metabolism-related genes between normal and DN samples. We classified DN into subtypes based on NAD gene expression and evaluated NAD scores using ssGSEA. Immune cell infiltration and pathway analyses were assessed using ssGSEA, Microenvironment Cell Populations-counter (MCPcounter), and Gene Set Variation Analysis (GSVA). Key biomarker genes were identified using machine learning algorithms and validated across multiple datasets. We further explored the relationship between gene expression and kidney function using the Nephroseq V5 tool. Thirteen differentially expressed NAD metabolism-related genes were identified, with distinctive expression patterns observed between normal and DN samples. Two distinct NAD-related subtypes were classified, demonstrating significant differences in gene expression, immune cell infiltration, and pathway activities. Immune-related pathways and cellular processes exhibited varied enrichment between subtypes. Six key NAD metabolism-related genes (FMO3, ALDH1A3, FMO5, TKT, LBR, HPGD) were identified as potential biomarkers. Higher levels of FMO3, ALDH1A3, TKT, and LBR were linked to worse kidney function, while FMO5 and HPGD were associated with better kidney function. The study highlights the significant involvement of NAD metabolism-related genes in DN pathogenesis and their association with disease subtypes and renal function. The identified biomarkers could be targets for new treatments and provide insight for future DN research.
Cyanide is an endogenous stimulator of endothelial cell proliferation, migration and differentiation.
Kieronska-Rudek A, Petrosino M, Zuhra K … +1 more , Szabo C
Exp Biol Med (Maywood) · 2026 · PMID 41658250 · Full text
Cyanide is generally considered a cytotoxic molecule. However, recent studies have shown that mammalian cells - including endothelial cells - can produce cyanide from glycine via a lysosomal pathway. Studies in hepatocyt...
Cyanide is generally considered a cytotoxic molecule. However, recent studies have shown that mammalian cells - including endothelial cells - can produce cyanide from glycine via a lysosomal pathway. Studies in hepatocytes indicated that cyanide, when administered at low concentrations, or when generated from endogenous sources, exerts regulatory, rather than cytotoxic effects. Here we show that human umbilical vein endothelial cells produce detectable levels of cyanide (∼0.1 nmoles/mg protein/h), and this is enhanced by administration of glycine (1 mM). Glycine stimulates endothelial cell proliferation, migration and tube formation. Low concentrations of the cyanide releasing molecules amygdalin or mandelonitrile (100 µM) exert similar effects. On one hand, cyanide induces the upregulation of VEGF protein in endothelial cells, while on the other hand, VEGF stimulates the generation of cyanide by endothelial cells, suggesting a positive feedback. VEGF-stimulated endothelial cell ATP generation, proliferation and migration is inhibited by the cyanide scavenger hydroxycobalamin (10 µM) as well as by pharmacological agents that prevent lysosomal acidification and thus inhibit cyanide formation by the endothelial cells. In conclusion, cyanide, at low concentrations, generated by endothelial cells, acts as a proangiogenic mediator, via stimulation of the VEGF pathway and the maintenance of cellular bioenergetics.
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