Experimental Biology And Medicine (Maywood, N.J.)[JOURNAL]
Sun
200 papers
Altered expression and correlation with the prognosis of diabetic nephropathy.
Injinari N, Hadizadeh M, Namiranian N … +3 more , Kalantar SM, Firoozabadi AD, Asadollahi S
Exp Biol Med (Maywood) · 2025 · PMID 41657662 · Full text
Although diabetic nephropathy (DN) stands as a prominent complication in individuals with diabetes, the specific molecular mechanisms remain unclear. In this study, we focused on one newly discovered lncRNA, , and its ta...
Although diabetic nephropathy (DN) stands as a prominent complication in individuals with diabetes, the specific molecular mechanisms remain unclear. In this study, we focused on one newly discovered lncRNA, , and its target gene, , in individuals with various levels of DN. Twenty-eight participants with different stages of DN (14 early stage and 14 late stage), 12 non-diabetic individuals, and 12 with T2DM without microvascular complications were selected. The qPCR was done, and one-way ANOVA assessed gene expression. ROC curves analysis and Spearman correlations between levels of expression and clinicopathological parameters were explored. The expression of decreased in the early and late DN groups compared to the type 2 diabetes (T2DM) (P = 0.01 and P = 0.03, respectively) and non-diabetic groups (P = 0.01 and P = 0.03, respectively). However, gene expression analysis revealed that there was no significant difference between the groups (P = 0.27). levels negatively correlated with microalbuminuria (P = 0.003, r = -0.41), but not with creatinine (Cr) (P = 0.058, r = -0.29). Moreover, there was no correlation between and microalbumin (P = 0.85, r = 0.02) and Cr (P = 0.49, r = 0.10). ROC curves underscored significant diagnostic accuracy for in distinguishing DN from people without kidney diseases (P < 0.05). This study introduces as a potential key player in the molecular landscape of DN, shedding light on its multifaceted interactions. The results provide a basis for further exploration and therapeutic interventions in the management of DN.
Functional roles of Keratin 6A in disease pathogenesis across cancer and skin disorders.
Su Y, Su S, Li M … +5 more , Zhang Z, Zhang S, Fan C, Luo W, Guo S
Exp Biol Med (Maywood) · 2026 · PMID 41648000 · Full text
Keratin 6A (KRT6A) is an epithelial-specific type II keratin localized within cytoskeletal intermediate filaments and functions in cooperation with KRT16/17 to maintain epidermal homeostasis and tissue repair. Accumulati...
Keratin 6A (KRT6A) is an epithelial-specific type II keratin localized within cytoskeletal intermediate filaments and functions in cooperation with KRT16/17 to maintain epidermal homeostasis and tissue repair. Accumulating evidence highlights its multifaceted roles in cancer. Aberrant KRT6A expression promotes cell cycle progression, epithelial-mesenchymal transition, migration, and invasion, thereby driving tumor initiation and metastasis, although tumor-suppressive effects have been observed in specific contexts. Mechanistically, KRT6A regulates adhesion, cytoskeletal remodeling, and critical signaling pathways, thereby reshaping tumor immunity and metabolism to facilitate immune evasion and metabolic dysregulation. Elevated KRT6A expression is strongly associated with resistance to chemotherapy, targeted therapy, and radiotherapy. Therapeutic approaches targeting KRT6A include nucleic acid-based interventions, protein degradation strategies, inhibition of upstream regulatory pathways, and combinatorial regimens to overcome drug resistance. Clinically, KRT6A has emerged as both a diagnostic and prognostic biomarker, supporting treatment monitoring and enhancing predictive models for risk stratification and individualized outcome evaluation. Beyond oncology, mutations in KRT6A underlie pachyonychia congenita, and its dysregulation contributes to epidermal hyperproliferative disorders such as psoriasis. Overall, systematic elucidation of the structure-function-pathway-clinical axis of KRT6A offers new opportunities for precision medicine and supports its potential as a therapeutic target in cancer management.
Liposomes as carriers for garlic oil delivery to increase anti-inflammatory and antioxidant activities in mice with ALI.
Hou R, Zhang X, Zhang J … +1 more , Zhang W
Exp Biol Med (Maywood) · 2026 · PMID 41647999 · Full text
ALI/ARDS are clinical syndromes with diverse etiological origins and are characterized by high mortality rates and a lack of specific therapeutic options. Garlic oil (GO) has been utilized in both culinary and medicinal...
ALI/ARDS are clinical syndromes with diverse etiological origins and are characterized by high mortality rates and a lack of specific therapeutic options. Garlic oil (GO) has been utilized in both culinary and medicinal applications for millennia. However, its complex chemical composition and inherent instability have limited further development and clinical application. We aimed to encapsulate GO within liposomes to increase its solubility and stability. The therapeutic efficacy of GO-loaded liposomes (GO-lips) against LPS-induced ALI was subsequently evaluated . A novel GO-lip formulation was developed, and its preparation process was optimized to ensure its stability and bioavailability. A murine model of LPS-induced ALI was established. The animals were randomly assigned to the normal control, LPS model, GO treatment, or GO-lip treatment group. Therapeutic outcomes were evaluated by lung tissue histopathology, inflammatory cytokine quantification and oxidative stress biomarker measurement. PCR and molecular dynamics simulations were used to verify the ALI treatment-related pathways influenced by GO-lips. We successfully developed GO-lips using a novel fabrication method. GO-lips demonstrated favorable physicochemical characteristics, with a mean particle diameter of 175 ± 3 nm, a PDI of 0.27 ± 0.02, and an encapsulation efficiency of 70.74 ± 2.11%. Compared with the LPS model group, the GO-lip treatment group exhibited significant protection against LPS-induced ALI. GO-lips demonstrated greater efficacy than free GO, as evidenced by the improved lung histopathology, reduced pulmonary edema, decreased inflammatory responses, and attenuated oxidative stress. PCR analysis demonstrated that GO-lips significantly protect mice primarily via Nrf2 pathway activation. These findings suggest that liposomal encapsulation of GO increases its anti-inflammatory and antioxidant activities, protecting against LPS-induced ALI. This research offers a novel clinical therapeutic approach for ALI and contributes to foundational knowledge supporting the development and utilization of GO-derived formulations.
HIV-HPV interactions via extracellular vesicles among tobacco smokers and nonsmokers.
Sinha N, Hiser L, Godse S … +5 more , Zhou L, Shynykul Z, Risley C, Cory T, Kumar S
Exp Biol Med (Maywood) · 2025 · PMID 41646506 · Full text
Human Immunodeficiency Virus (HIV) and Human Papillomavirus (HPV) co-infections are significantly prevalent, especially among African Americans (AA), a situation further compounded by the prevalence of tobacco smoking. E...
Human Immunodeficiency Virus (HIV) and Human Papillomavirus (HPV) co-infections are significantly prevalent, especially among African Americans (AA), a situation further compounded by the prevalence of tobacco smoking. Extracellular vesicles (EVs) are integral to the mechanisms of viral pathogenesis, as they are pivotal in the modulation of immune responses and the inflammatory process. This research study examines the varying concentrations of EVs, their associated biomarkers, and the cytokine/chemokine profiles present in plasma obtained from individuals infected with HIV and those coinfected with HIV and HPV, with particular emphasis on the ramifications of smoking behavior. Our findings revealed that HIV infection markedly elevates EV formation and modifies their protein composition, whereas HPV co-infection does not significantly augment EV levels but does influence the specific cytokine packaging. Notably, monocyte chemoattractant protein-1 (MCP-1 or CCL2) and Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES or CCL5) exhibited substantial enrichment in EVs derived from individuals coinfected with HIV and HPV, implying a potential role of EVs in immune modulation related to viral persistence. Importantly, smoking was found to affect EV characteristics, resulting in an increase in EV size and the packaging of inflammatory mediators, such as MCP-1 and interleukin-18 (IL-18), from plasma into EVs in HIV- and/or HIV+HPV-infected samples. This observation suggests that oxidative stress induced by smoking may intensify immune dysregulation through modifications in EV-mediated cytokine signaling pathways. Nevertheless, smoking did not exhibit a significant impact on the expression of EV marker proteins or the overall levels of EVs. These outcomes underscore the intricate interactions between HIV, HPV, and/or smoking in influencing the immune milieu via EVs. Further comprehensive understanding of the role of EVs in the context of these viral infections could yield valuable insights into potential biomarkers for disease progression and new therapeutic strategies.
The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.
Wang N, Luo L, Yang X
Exp Biol Med (Maywood) · 2026 · PMID 41641369 · Full text
Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for...
Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.
The correlation between pro- and anti-inflammatory cytokines and anti-spike IgG antibody responses induced by the SARS-CoV-2 coronavirus vaccine.
Salman MA, Jameel TY, Ayvaz A … +1 more , Abdullah AR
Exp Biol Med (Maywood) · 2025 · PMID 41613365 · Full text
Even with the development of the Pfizer-BioNTech BNT162b2 vaccine, which provides protection against COVID-19 and demonstrates high efficacy in generating immune responses, the complexities of the dynamics linking pro- a...
Even with the development of the Pfizer-BioNTech BNT162b2 vaccine, which provides protection against COVID-19 and demonstrates high efficacy in generating immune responses, the complexities of the dynamics linking pro- and anti-inflammatory cytokine profiles with anti-spike IgG production remain unclear. The study aims to elucidate these immune dynamics after vaccination. This prospective cohort research was done at the University of Diyala from January 2022 to January 2023, evaluating the immunological response to the Pfizer-BNT162b2 mRNA vaccine in 180 healthy students. Pro- and anti-inflammatory cytokines and anti-spike IgG antibodies were measured before vaccination, 1 month after the second dose, and 4 months after the second dose. Biomarkers were analyzed via ELISA and CRP assays. The study involved 180 healthy participants (80 males, 100 females; median age, 21 years; BMI, 25.7 kg/m). After the first Pfizer-BNT162b2 vaccine dose, the level of anti-spike IgG increased by 330-fold, and the levels of pro- and anti-inflammatory markers, such as IL-1β, IL-10, and CRP, increased significantly. Four months after the second dose, anti-spike IgG levels were 136-fold above baseline. Significant correlations emerged between cytokine and IgG levels, with anti-spike IgG/IL-10 ratios elevated and sustained over the long term. Pfizer-BNT162b2 vaccine elicits a significant immune response associated with changes in pro-inflammatory cytokines, and the interaction between these cytokines and anti-spike IgG suggests a potential role for immune regulation in enhancing humoral immunity. Based on these findings, the IgG/IL-17 ratio may serve as a viable exploratory biomarker for assessing short- and medium-term vaccination efficacy.
Machine learning-based comprehensive analysis of m6A RNA methylation regulators in colorectal cancer: implications for prognosis, immune microenvironment, and immunotherapy response.
Kong F, Feng J, Shan H … +2 more , Zhu Y, Zhu LJ
Exp Biol Med (Maywood) · 2025 · PMID 41613364 · Full text
N6-methyladenosine (m6A) RNA methylation regulators have been implicated in colorectal cancer (CRC) progression. However, systematic evaluation using multiple machine learning approaches for prognostic prediction remains...
N6-methyladenosine (m6A) RNA methylation regulators have been implicated in colorectal cancer (CRC) progression. However, systematic evaluation using multiple machine learning approaches for prognostic prediction remains limited. This study aimed to develop and validate machine learning models for CRC prognosis based on m6A regulators and assess their potential for immunotherapy response prediction. We analyzed 1,047 CRC patients from TCGA and GEO databases (70% training, 30% validation). Twenty machine learning algorithms were systematically evaluated, with LASSO regression selecting optimal features from 27 m6A regulators. SHAP analysis provided model interpretability. Immune microenvironment characterization and immunotherapy response prediction were performed using established computational methods. LASSO regression selected eight m6A regulators (IGF2BP2, METTL3, HNRNPA2B1, METTL14, YTHDF2, VIRMA, FTO, ALKBH5) for model construction. Among 20 algorithms tested, Random Forest achieved optimal performance (training AUC = 0.895, validation AUC = 0.847). SHAP analysis identified IGF2BP2 (mean |SHAP| = 0.42) and METTL3 (mean |SHAP| = 0.36) as primary contributors to risk prediction. Risk stratification showed significant survival differences (HR = 2.41, 95% CI: 1.73-3.36, p < 0.001). Low-risk patients demonstrated enhanced immune infiltration with higher CD8 T cells (17.8% vs. 10.2%, p < 0.001) and better predicted immunotherapy response rates (36.5% vs. 20.3%, p = 0.006). Our systematic machine learning analysis demonstrates that m6A regulators can effectively predict CRC prognosis and immunotherapy response. The eight-gene signature provides a practical tool for clinical risk assessment and treatment decision-making.
Inflammatory indicators derived from complete blood counts in relation to osteoarthritis prevalence: findings from the NHANES 2007-2020 cross-sectional survey.
Ye Z, Zhao T, Huang X … +10 more , Song Y, Cheng L, Liu Y, Qiu M, Long R, Chen W, Wang Y, Xie H, Fan L, Hu X
Exp Biol Med (Maywood) · 2025 · PMID 41607949 · Full text
Although multiple studies have confirmed the importance of chronic low-grade inflammation in the development of osteoarthritis (OA), the association between complete blood count (CBC)-derived inflammatory indicators and...
Although multiple studies have confirmed the importance of chronic low-grade inflammation in the development of osteoarthritis (OA), the association between complete blood count (CBC)-derived inflammatory indicators and osteoarthritis prevalence remains unclear. The present study aims to explore the association between CBC-derived inflammatory indicators and OA prevalence. We used NHANES data from 2007 to 2020 for a cross-sectional analysis. Multivariate logistic regression models were used to evaluate the association between CBC-derived inflammatory indicators and OA prevalence. Restricted cubic spline function (RCS) and threshold analysis were used to assess potential nonlinear associations. In addition, subgroup and sensitivity analyses were performed to assess the stability of the results. Finally, we used LASSO regression to identify the variables most associated with OA outcomes to construct a prediction model, and the model's validity was verified. Among the 24,112 patients in this study, 3,195 were diagnosed with OA. In the adjusted model, multivariate logistic regression analysis showed that 5 inflammatory indicators (SII, SIRI, MLR, NMLR, NLR) were positively associated with OA prevalence. RCS and threshold analysis showed nonlinear associations between (SII, NMLR, NLR) and OA prevalence. After variable screening, we established an OA risk prediction model with an area under the curve (AUC) of 0.735 (95% CI: 0.726-0.744). Both the decision and calibration curve showed that the model had good clinical significance. The Present study suggests that CBC-derived inflammatory indicators are statistically associated with OA prevalence. Furthermore, MLR and NMLR could be valuable predictors of OA and offer novel perspectives on its assessment and treatment.
Tear proteomic analysis in keratoconus patients and potential biomarkers: a case-control study.
de Almeida Borges D, Alborghetti MR, Domingues RR … +2 more , Paes Leme AF, Alves M
Exp Biol Med (Maywood) · 2025 · PMID 41601845 · Full text
Keratoconus is a corneal ectasia whose pathophysiological mechanisms, including biomolecular alterations and genetic influences, remain poorly understood. Recent studies have shown altered cytokine levels, increased prot...
Keratoconus is a corneal ectasia whose pathophysiological mechanisms, including biomolecular alterations and genetic influences, remain poorly understood. Recent studies have shown altered cytokine levels, increased proteinase activity, and other potential mediators in the tear film and corneal tissue, highlighting a possible involvement of inflammatory pathways in the pathophysiology of keratoconus. This observational study aims to characterize the tear proteome of keratoconus patients and compare it to a control group, reporting potential disease biomarkers in the tear film. 23 keratoconus patients were selected at the Cornea and External Diseases Outpatient Clinic of the Clinics Hospital of UNICAMP. The control group consisted of 17 age- and sex-matched participants. All study subjects underwent corneal tomography (Pentacam). Tear film samples were collected and sent for proteomic evaluation by mass spectrometry at the National Biosciences Laboratory (LNBio). After quantification, univariate and multivariate statistical analyses were performed. A total of 353 proteins were identified and quantified, of which 25 showed statistical differences in the univariate analysis (t-test), and 19 were selected in the multivariate analysis (PLS-DA). There was an overlap of 7 proteins identified in both uni- and multivariate analyses: chitinase-3-like protein 2, prosaposin, zymogen granule protein 16 homolog B, procollagen-lysine,2-oxoglutarate 5-dioxygenase 1, secretoglobin family 1D member 1, albumin, and Ig kappa chain V-I region. Thirty-seven proteins showed statistically significant variation between the keratoconus and control groups. Proteomic analysis revealed differentially expressed proteins in the tear film of keratoconus patients. We report the identified proteomic profile, which includes potential biomarkers that may help elucidate the disease's pathophysiology.
Beginning of a new era of synthetic messenger RNA therapeutics: Comprehensive insights on mRNA drug design, development and applications.
Heendeniya SN, Chen S, Bhatti S … +5 more , Zahra QUA, Rahimizadeh K, Poudel BH, Wilton SD, Veedu RN
Exp Biol Med (Maywood) · 2025 · PMID 41586257 · Full text
Messenger RNA (mRNA) therapeutics have significantly transformed contemporary medicine, particularly through their role as the active component in the SARS-CoV-2 vaccine. This remarkable achievement is the culmination of...
Messenger RNA (mRNA) therapeutics have significantly transformed contemporary medicine, particularly through their role as the active component in the SARS-CoV-2 vaccine. This remarkable achievement is the culmination of extensive research conducted over many years by scientists. The widespread administration of the COVID-19 vaccine has further accelerated research into the precise therapeutic potential of mRNA technologies. Since mRNA doesn't integrate with the host genome, the safety and versatility of mRNA-based therapeutics make them an iconic candidate in targeted therapies. Due to a surge in innovation efforts, biomodification of the molecular signatures of mRNAs like the 5'cap, untranslated regions (UTRs), and the poly(A) tail are being developed to increase translation efficacy. Recent advancements in chemical modifications, codon optimization techniques, and targeted delivery methods have significantly enhanced the stability of synthetic mRNAs while concurrently reducing their immunogenicity. Various mRNA manufacturing and synthesizing methods are investigated in this review, focusing on their scalability and limitations. mRNA therapeutic strategies can be divided into protein replacement, immune modulation, and cellular modulation. This review explores mRNA's molecular landscape and comprehensive utility, including applications in both clinical trials and commercial sectors.
Neutrophil extracellular traps: emerging drivers and therapeutic targets in abdominal aortic aneurysm pathogenesis.
Lyu X, Liu Q, Shi J … +2 more , Chen Y, Dai X
Exp Biol Med (Maywood) · 2025 · PMID 41574096 · Full text
Abdominal aortic aneurysm (AAA) is a life-threatening condition with no effective pharmacological treatments, underscoring the critical need to identify novel therapeutic targets. Emerging translational and clinical evid...
Abdominal aortic aneurysm (AAA) is a life-threatening condition with no effective pharmacological treatments, underscoring the critical need to identify novel therapeutic targets. Emerging translational and clinical evidence implicates neutrophil extracellular traps (NETs) as potential drivers of AAA pathogenesis. This review systematically delineates the mechanisms by which NETs contribute to aortic wall degradation, focusing on their direct cytotoxicity to vascular smooth muscle cells (VSMCs), induction of VSMC phenotypic switching and ferroptosis, amplification of inflammatory cascades, and propagation of thromboinflammation. Key mediators include PAD4, IL-1β, PI3Kγ, neutrophil elastase, myeloperoxidase, and mitochondrial DNA. NET components (citrullinated histone H3, cell-free DNA, neutrophil elastase) serve as promising diagnostic and prognostic biomarkers. Preclinical studies highlight the efficacy of NET-targeting strategies, including inhibiting NET formation, degrading existing NETs, neutralizing cytotoxic components, and modulating downstream pathways (e.g., with ferroptosis inhibitors). Nanotechnology platforms enhance site-specific delivery of these agents. By integrating the research background with its practical implications, we conclude that targeting NETs represents a promising paradigm shift. Despite translational challenges, this approach offers a rational framework for developing the first pharmacotherapies aimed at stabilizing AAA and addressing a major unmet clinical need.
LncRNA HOTAIR promotes LPS-induced inflammatory responses by activating the NF-κB pathway.
Zhu F, Mo Z, Lin W … +10 more , Sun C, Huang X, Ye M, He H, Li Y, Wang K, Zhu J, Lin C, Wei S, Liang Z
Exp Biol Med (Maywood) · 2025 · PMID 41567340 · Full text
Acute lung injury (ALI) is a disease with an excessive inflammatory response triggered by activating the NF-κB signaling pathway. Our study aims to investigate the role of the long non-coding RNA HOTAIR in ALI-associated...
Acute lung injury (ALI) is a disease with an excessive inflammatory response triggered by activating the NF-κB signaling pathway. Our study aims to investigate the role of the long non-coding RNA HOTAIR in ALI-associated hyperinflammation, providing evidence for HOTAIR as a potential therapeutic target for ALI. Here, we examined the contribution of HOTAIR to LPS-induced lung injury using both A549 cell and murine models. LPS stimulation markedly increased HOTAIR expression in A549 cells, accompanied by reduced cell viability and elevated secretion of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Overexpression of HOTAIR further amplified NF-κB signaling, as indicated by increased phosphorylation of IκBα and p65 and enhanced nuclear translocation of p65, whereas silencing HOTAIR effectively reversed these effects. , knockdown of HOTAIR significantly mitigated LPS-induced lung injury, reduced inflammatory cytokine production, and suppressed NF-κB activation in mice. Our findings reveal the contribution of HOTAIR to NF-κB-driven inflammatory injury in ALI, offering insight into its regulatory role and informing future exploration of targeted therapeutic approaches.
Diet-lifestyle oxidative balance in relation to cardiometabolic multimorbidity: findings from the national health and nutrition examination survey.
Shi W, Zhao Y, Park J … +1 more , Chen W
Exp Biol Med (Maywood) · 2025 · PMID 41488875 · Full text
Oxidative stress is a critical factor in the development of cardiometabolic diseases. The Oxidative Balance Score (OBS), integrating dietary and lifestyle factors, has been proposed as a measure of the balance between pr...
Oxidative stress is a critical factor in the development of cardiometabolic diseases. The Oxidative Balance Score (OBS), integrating dietary and lifestyle factors, has been proposed as a measure of the balance between pro-oxidants and antioxidants. This study aims to explore the relationship between OBS and prevalent cardiometabolic multimorbidity (CMM), and to evaluate whether adding OBS into clinical practice is associated with better CMM identification in the general population. A total of 26,191 participants were selected from the National Health and Nutrition Examination Survey. CMM was defined as having a history of two or more conditions: diabetes mellitus, stroke, or coronary heart disease. The prevalence of CMM was 2.95%. After adjusting for demographic, anthropometric, laboratory, and medical history data, each standard deviation increase in OBS was associated with a 26.1% reduction in the risk of prevalent CMM. Participants in the highest quartile of OBS had a 0.530-fold risk of prevalent CMM compared to those in the lowest quartile. Smooth curve fitting indicated a proportional reduction in CMM risk with increasing OBS. Sensitivity analysis confirmed significant associations between both dietary and lifestyle OBS with prevalent CMM. ROC analysis revealed that incorporating OBS into conventional cardiometabolic risk factors was associated with a slight improvement in CMM identification (AUC: 0.912 vs. 0.916, P = 0.001). Reclassification analysis further indicated the incremental value of OBS. This study revealed a negative, linear, and robust association between OBS and prevalent CMM in the general population. However, reverse causation cannot be ruled out. Future studies should use longitudinal or Mendelian randomization approaches to establish causality.
Protective effects of berberine-loaded chitosan/solid lipid nanoparticles in streptozotocin-induced gestational diabetes mellitus rats.
Liu Y, Hussain SA, Yue H
Exp Biol Med (Maywood) · 2025 · PMID 41488874 · Full text
Berberine, known as an antioxidant agent, can improve glycemic indices in animal models of diabetes; however, it is clinically limited by poor bioavailability. Nanoparticles show the desirable capacity as delivery platfo...
Berberine, known as an antioxidant agent, can improve glycemic indices in animal models of diabetes; however, it is clinically limited by poor bioavailability. Nanoparticles show the desirable capacity as delivery platforms for improving the bioavailability of medicinal agents. Here, we aimed to enhance the bioavailability and therapeutic impacts of berberine in streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) rats by its encapsulation into the chitosan-coated solid lipid nanoparticles (SLNs) formulation. Berberine-loaded chitosan/SLN nanoparticles were formulated by the solvent-injection approach followed by a homogenization operation. The particle size, surface charge, and polydispersity index, as well as encapsulation efficiency percent (EE%), stability and berberine release, and pharmacokinetics were studied. Glycemic indices, such as fasting glucose and insulin, oral glucose tolerance, insulin tolerance, and homeostasis model of insulin resistance (HOMA-IR) scores, as well as the activity level of liver antioxidant and pro-oxidant enzymes, were evaluated in STZ-induced GDM rats. The particle size of berberine-loaded chitosan/SLN formulation was detected in the nano-range with high stability and high EE% as well as a sustained-release profile. Berberine nanoparticle treatment could provide a significantly higher oral bioavailability of berberine in experimental rats. Berberine nanoparticles remarkably reversed the altered glycemic indices, body weight, and pro-oxidant/antioxidant balance in STZ-induced GDM rats, with significantly higher effects than free berberine. In conclusion, chitosan-coated SLN nanoparticles firmly enhanced the therapeutic impacts of berberine on STZ-induced GDM, suggesting chitosan-coated SLN nanoparticles as an efficient oral delivery system for enhancing the bioavailability of berberine and, thus, improving its pharmacological impacts.
Chimeric antigen receptor natural killer cell therapy for solid tumors: mechanisms, clinical progress, and strategies to overcome the tumor microenvironment.
Xiang Y, Dong J, Shao L … +1 more , Chen S
Exp Biol Med (Maywood) · 2025 · PMID 41488873 · Full text
Natural killer (NK) cells represent a fundamental component of the innate immune system, endowed with the ability to identify and eradicate virus-infected and malignant cells. The advent of chimeric antigen receptor (CAR...
Natural killer (NK) cells represent a fundamental component of the innate immune system, endowed with the ability to identify and eradicate virus-infected and malignant cells. The advent of chimeric antigen receptor (CAR) technology has introduced innovative strategies for augmenting the antitumor potential of natural killer (NK) cells. Chimeric antigen receptor natural killer (CAR-NK) cells exert dual cytotoxic effects against tumor cells through CAR-mediated antigen-specific recognition in concert with the nonspecific cytolytic activity mediated by intrinsic NK receptors. This review critically evaluates the clinical progression of CAR-NK cells specifically against solid tumors, focusing on mechanisms to overcome the immunosuppressive tumor microenvironment (TME), the complexity of allogeneic manufacturing, and the latest engineering strategies for enhanced homing and persistence. Specifically, we emphasize the urgent need for robust Phase II/III clinical data and standardized Good Manufacturing Practice (GMP) protocols to realize the full potential of off-the-shelf allogeneic CAR-NK therapies. Additionally, we examine technological advancements and emerging directions addressing persistent challenges in this domain to offer theoretical underpinnings and research perspectives for the clinical deployment of CAR-NK cell therapy in solid tumor management.
Mapping microglial mechanisms in Alzheimer's disease: a comprehensive analysis.
Wang X, Guo Y, Zha Y … +3 more , Wang S, Yang W, Jia Q
Exp Biol Med (Maywood) · 2025 · PMID 41445867 · Full text
Microglia, the brain's primary immune cells, play crucial roles in Alzheimer's disease (AD) pathogenesis. However, existing research remains abundant yet fragmented. Therefore, this study aimed to systematically identify...
Microglia, the brain's primary immune cells, play crucial roles in Alzheimer's disease (AD) pathogenesis. However, existing research remains abundant yet fragmented. Therefore, this study aimed to systematically identify hotspots and trends in microglia-related AD research, while providing an in-depth analysis of the underlying mechanisms to advance mechanistic understanding and therapeutic development. To achieve this, articles on microglia in AD were retrieved from the Web of Science Core Collection (WoSCC) database, and bibliometric analysis was performed using the WoSCC platform and CiteSpace 6.3.R1, with a focus on global collaboration, institutional and journal contributions, keyword bursts, and high-impact articles to comprehensively elucidate the underlying mechanisms. In total, 1,043 articles from 67 countries and regions were included.Among them, the United States led with 484 articles and an H-index of 100, followed by China with 276 articles. The University of California system (77 articles) and Harvard University (74 articles) had the highest H-index, both at 41. Journal of Neuroinflammation published the most articles (57 articles). Burst keywords persisting until 2024 included "memory," "NLRP3 inflammasome," and "system." High-impact studies emphasized microglial roles in AD pathology, including Aβ clearance, synaptic pruning, inflammation, metabolism, phenotype shifts, immune memory, and genetic variation. Overall, microglial mechanisms are at the forefront of AD research. The United States leads in both article number and influence, followed by China. The University of California system and Harvard University demonstrate the greatest output and impact. is the leading journal. Microglial NLRP3 activation, system-level interactions, and memory impairment have emerged as key research hotspots in AD. Future research will focus on microglial mechanisms and therapeutic targets in AD.
Peripheral artery disease and local drug delivery: a review of disease pathology and drug delivery systems for therapy below the knee.
Akers NM, Dugas TR
Exp Biol Med (Maywood) · 2025 · PMID 41439172 · Full text
Peripheral artery disease (PAD) is a disease of both atherosclerotic and thromboembolic pathology, affecting more than 230 million people globally. PAD patients are at an increased risk of thrombotic events and often req...
Peripheral artery disease (PAD) is a disease of both atherosclerotic and thromboembolic pathology, affecting more than 230 million people globally. PAD patients are at an increased risk of thrombotic events and often require lifelong antithrombotic therapy. Thromboembolism can lead to complete occlusion of affected arteries and put patients at risk for critical limb threatening ischemia (CTLI). PAD blockages are cleared using drug-eluting stents (DES) and drug-coated balloons (DCB). However, PAD treatment below the knee (BTK) presents unique challenges. While DCB are frequently used to treat BTK disease, no DCB has gained FDA approval for this indication. However, innovation in the field has produced drug delivery systems and formulations that may yet enhance the effectiveness of these therapies. In this review, we will provide a brief overview of the pathological mechanisms associated with PAD and review the materials and drugs frequently used in DCBs with an emphasis on excipients and drug carriers. Finally, we will highlight emerging devices undergoing clinical trials to treat BTK disease and how they differ from their predecessors.
Clinical data comparison for FDA-approved gene therapies in sickle cell disease.
Leonard A, Kanter J
Exp Biol Med (Maywood) · 2025 · PMID 41439171 · Full text
Sickle cell disease (SCD) is a severe inherited hemoglobinopathy with limited curative treatment options. In December 2023, the U.S. FDA approved two autologous gene therapies, lovo-cel (bluebird bio) and exa-cel (Vertex...
Sickle cell disease (SCD) is a severe inherited hemoglobinopathy with limited curative treatment options. In December 2023, the U.S. FDA approved two autologous gene therapies, lovo-cel (bluebird bio) and exa-cel (Vertex/CRISPR Therapeutics), offering potentially transformative outcomes. We performed a comparative analysis of these therapies based on published clinical trial design, patient eligibility, manufacturing requirements, and reported efficacy and safety outcomes. Overall, participants treated with lovo-cel had more severe baseline disease, reflected by a higher median rate of vaso-occlusive events (VOEs), despite the use of a more stringent VOE definition. Mobilization of hematopoietic stem cells (HSCs) with single-agent plerixafor proved challenging in both trials, with most participants requiring multiple mobilization and apheresis cycles. A greater proportion of exa-cel participants required three or more apheresis procedures, driven by higher CD34 cell dose targets needed to compensate for CRISPR-associated HSC loss. Both therapies demonstrated greater than 90% resolution of severe VOEs, with near-complete resolution in pediatric participants. A small subset of participants experienced VOEs post-treatment, including events occurring beyond the primary efficacy assessment period. Notably, no recurrent strokes were reported among lovo-cel treated participants with a history of overt stroke. Both therapies provide durable, clinically meaningful benefit and represent a major advancement in SCD management. However, differences in trial populations, cell collection logistics, and manufacturing have important implications for real-world applications. Continued long-term follow-up and the establishment of standardized post-treatment registries will be critical to fully assess durability, monitor late effects, and inform patient selection.
ApoE COG 133 mimetic peptide improves survival, infection burden, and toxin-A-induced intestinal damage in mice.
de Azevedo OGR, Shin JH, Freire RS … +6 more , Ciurleo GCV, Brito GAC, Vitek MP, Guerrant RL, Oriá RB, Warren CA
Exp Biol Med (Maywood) · 2025 · PMID 41416135 · Full text
Apolipoprotein E (ApoE = protein; APOE = gene), a lipid carrier that modulates inflammatory responses, may influence () infection (CDI) outcomes. We explored the role of the APOE gene using apoE-deficient mice challenge...
Apolipoprotein E (ApoE = protein; APOE = gene), a lipid carrier that modulates inflammatory responses, may influence () infection (CDI) outcomes. We explored the role of the APOE gene using apoE-deficient mice challenged by toxin A (TcdA)-induced enteritis, and the potential use of the ApoE mimetic peptide in repairing the intestinal damage induced by TcdA. 4-cm ileal loops from C57BL/6 wild-type and APOE knockout (-/-) were ligated and injected with either PBS or TcdA (50 µg). After 4 h of incubation, the intestinal loops were harvested for measurement of length, weight, volume of secretion, and histopathology scores. In mouse ileal loops, TcdA induced a significant increase in weight/ileal loop length in the wild-type mice. When APOE mice were infected with 1 × 10-10 CFUs of , they had higher deaths and diarrhea scores compared to wild-type. APOE mice under the toxin A (TcdA) had worse inflammatory changes in the ileal loop. APOE mice treated with COG133 (3 mg/kg) showed fewer deaths, and lower diarrhea scores, but no change in shedding. This suggests a potential anti-inflammatory role of COG133 in CDI. More studies are neede to these intial findings in depth.
Characterisation of the function of a lncRNA containing SINE-VNTR-Alu 67 to regulate the genes at the locus.
Piacentini K, Fröhlich A, Pfaff A … +1 more , Kõks S
Exp Biol Med (Maywood) · 2025 · PMID 41394315 · Full text
Parkinson's disease (PD) is a complex neurodegenerative disease that involves many interlinking pathways and genetic elements that remain to be fully understood and characterised. Non-coding genetic elements have long be...
Parkinson's disease (PD) is a complex neurodegenerative disease that involves many interlinking pathways and genetic elements that remain to be fully understood and characterised. Non-coding genetic elements have long been overlooked, however recent advancements in the field have highlighted their importance with an area of interest being transposable elements. SINE-VNTR-Alu (SVA) elements are the youngest and smallest subset of retrotransposons that are only found within hominid species. SVAs have been shown to have strong regulatory impacts within our genome and can affect progression of neurodegenerative disease such as PD. Previous studies identified an SVA, polymorphic for its presence/absence, that was associated with changes in gene expression at the locus. This particular SVA is located within a long non-coding RNA (lncRNA) and is known as SVA_67. Here, we evaluated the SVA67-lncRNA effects on gene expression within the locus, a region associated with several neurodegenerative diseases in the SH-SY5Y cell line. The expression of SVA67-lncRNA in the SH-SY5Y cell line was associated with differential expression of several genes at the locus including , , , , and . This study provides the first analysis of this SVA67-lncRNA and potential evidence for its involvement in complex diseases, such as PD.
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