Experimental Biology And Medicine (Maywood, N.J.)[JOURNAL]
Sun
200 papers
Clinical characteristics and prognosis of ALL in children with CDKN2A/B gene deletion.
Wang Y, Wu P, Mao X … +5 more , Jiang N, Huang Y, Zhang L, Liu L, Tian X
Exp Biol Med (Maywood) · 2025 · PMID 40017529 · Full text
This study aimed to explore the correlation between the deletion of the CDKN2A/B gene and the prognosis of pediatric acute lymphoblastic leukemia (ALL) patients. A total of 310 pediatric patients who were diagnosed with...
This study aimed to explore the correlation between the deletion of the CDKN2A/B gene and the prognosis of pediatric acute lymphoblastic leukemia (ALL) patients. A total of 310 pediatric patients who were diagnosed with acute lymphoblastic leukemia at our hospital from January 2020 to September 2023 were included in this study. Among them, 78 patients with CDKN2A/B deletion were included in the final analysis. Additionally, 78 ALL patients without CDKN2A/B deletion, who were diagnosed during the same period, were randomly selected for comparison. A statistical analysis was conducted to compare the clinical characteristics and prognosis between the CDKN2A/B deletion group and the non-deletion group in ALL patients. The results showed that pediatric ALL patients with CDKN2A/B deletion had higher white blood cell counts and a greater proportion of immature cells in peripheral blood at diagnosis. The age at diagnosis was older in the deletion group, with a greater proportion in the >10-year-old group. CDKN2A/B deletion occurred more frequently in pediatric patients with T-ALL than in pediatric patients with B-ALL. Patients with CDKN2A/B deletion were more likely to have positive BCR-ABL1 expression combined with IKZF1 deletion. The overall survival (OS) rate was 89.7%, and the event-free survival (EFS) rate was 83.3% in the CDKN2A/B deletion group, which was lower than the OS rate of 97.4% and EFS rate of 93.6% in the non-deletion group. These results suggest that CDKN2A/B deletion may be one of the factors affecting poor prognosis. It provides a new perspective for clinical treatment, risk stratification, and prognostic assessment in pediatric ALL patients.
A study on the differences in the gut microbiota and metabolism between male and female mice in different stress periods.
Qiao Y, Guo J, Xiao Q … +6 more , Wang J, Zhang X, Liang X, Wei L, Bi H, Gao T
Exp Biol Med (Maywood) · 2025 · PMID 40008145 · Full text
The sex difference in depression has long been an unsolved issue. Women are twice as likely to suffer from depression as men. However, there were significant differences in the composition of gut microbiota between women...
The sex difference in depression has long been an unsolved issue. Women are twice as likely to suffer from depression as men. However, there were significant differences in the composition of gut microbiota between women and men. There is a lack of studies linking sex differences in depression to microbiota, and the specific mechanisms of this process have not been explained in detail. The main purpose of this study was to explore the gender differences in the intestinal tract of male and female depressed mice. In this study, chronic restraint stress (CRS) mouse models were used to simulate chronic stress, and behavioral tests were conducted, including the open field test (OFT), tail suspension test (TST) and forced swimming test (FST). Microbial diversity analysis and metabolomics were performed on collected mouse feces. The results showed that female mice were highly active and prone to anxious behavior before stress, and the levels of and 16α-hydroxyestrone were significantly different from those in male mice. After 21 days (Days) of stress, female mice showed depression-like behavior, and the levels of , 5α-pregnane-3,20-dione, and 2-hydroxyestradiol were significantly different from those in male mice. After 14 days of stress withdrawal, the depression-like behavior continued to worsen in female mice, and the levels of 5α-pregnane-3,20-dione, estrone glucuronide and were significantly different from those in male mice. In summary, female mice have stronger stress sensitivity and weaker resilience than male mice, which may be related to differences in bacterial diversity and estrogen metabolism disorders.
Bone marrow immune cells and drug resistance in acute myeloid leukemia.
Zhang M, Yang Y, Liu J … +3 more , Guo L, Guo Q, Liu W
Exp Biol Med (Maywood) · 2025 · PMID 40008144 · Full text
In recent years, the relationship between the immunosuppressive niche of the bone marrow and therapy resistance in acute myeloid leukemia (AML) has become a research focus. The abnormal number and function of immunosuppr...
In recent years, the relationship between the immunosuppressive niche of the bone marrow and therapy resistance in acute myeloid leukemia (AML) has become a research focus. The abnormal number and function of immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), along with the dysfunction and exhaustion of immunological effector cells, including cytotoxic T lymphocytes (CTLs), dendritic cells (DCs) and natural killer cells (NKs), can induce immune escape of leukemia cells and are closely linked to therapy resistance in leukemia. This article reviews the research progress on the relationship between immune cells in the marrow microenvironment and chemoresistance in AML, aiming to provide new ideas for the immunotherapy of AML.
MONet: cancer driver gene identification algorithm based on integrated analysis of multi-omics data and network models.
Ren Y, Zhang T, Liu J … +6 more , Ma F, Chen J, Li P, Xiao G, Sun C, Zhang Y
Exp Biol Med (Maywood) · 2025 · PMID 39968416 · Full text
Cancer progression is orchestrated by the accrual of mutations in driver genes, which endow malignant cells with a selective proliferative advantage. Identifying cancer driver genes is crucial for elucidating the molecul...
Cancer progression is orchestrated by the accrual of mutations in driver genes, which endow malignant cells with a selective proliferative advantage. Identifying cancer driver genes is crucial for elucidating the molecular mechanisms of cancer, advancing targeted therapies, and uncovering novel biomarkers. Based on integrated analysis of Multi-Omics data and Network models, we present MONet, a novel cancer driver gene identification algorithm. Our method utilizes two graph neural network algorithms on protein-protein interaction (PPI) networks to extract feature vector representations for each gene. These feature vectors are subsequently concatenated and fed into a multi-layer perceptron model (MLP) to perform semi-supervised identification of cancer driver genes. For each mutated gene, MONet assigns the probability of being potential driver, with genes identified in at least two PPI networks selected as candidate driver genes. When applied to pan-cancer datasets, MONet demonstrated robustness across various PPI networks, outperforming baseline models in terms of both the area under the receiver operating characteristic curve and the area under the precision-recall curve. Notably, MONet identified 37 novel driver genes that were missed by other methods, including 29 genes such as APOBEC2, GDNF, and PRELP, which are corroborated by existing literature, underscoring their critical roles in cancer development and progression. Through the MONet framework, we successfully identified known and novel candidate cancer driver genes, providing biologically meaningful insights into cancer mechanisms.
Is platelet-rich plasma better than steroids as epidural drug of choice in lumbar disc disease with radiculopathy? Meta-analysis of randomized controlled trials.
Muthu S, Viswanathan VK, Gangadaran P
Exp Biol Med (Maywood) · 2025 · PMID 39968415 · Full text
The current meta-analysis was performed to analyze the efficacy and safety of platelet-rich plasma (PRP) as an epidural injectate, in comparison with steroids in the management of radiculopathy due to lumbar disc disease...
The current meta-analysis was performed to analyze the efficacy and safety of platelet-rich plasma (PRP) as an epidural injectate, in comparison with steroids in the management of radiculopathy due to lumbar disc disease (LDD). We conducted independent and duplicate searches of the electronic databases (PubMed, Embase and Cochrane Library) in March 2024 to identify randomized controlled trials (RCTs) analyzing the efficacy of epidural PRP for pain relief in the management of LDD. Animal or studies, clinical studies without a comparator group, and retrospective or non-randomised clinical studies were excluded. Diverse post-intervention pain scores [visual analog score (VAS)] and functional scores [Oswestry Disability Index (ODI), SF-36], as reported in the reviewed studies, were evaluated. Statistical analysis was performed using STATA 17 software. 5 RCTs including 310 patients (PRP/Steroids = 153/157) were included in the analysis. The included studies compared the efficacy and safety of epidural PRP and steroids at various time-points including 1, 3, 6, 12, 24, and 48 weeks. Epidural PRP injection was found to offer comparable pain relief (VAS; WMD = -0.09, 95% CI [-0.66, 0.47], p = 0.641; I = 96.72%, p < 0.001), functional improvement (ODI; WMD = 0.72, 95% CI [-6.81, 8.25], p = 0.524; I = 98.73%, p < 0.001), and overall health improvement (SF-36; WMD = 1.01, 95% CI [-1.14, 3.17], p = 0.224; I = 0.0%, p = 0.36) as epidural steroid injection (ESI) at all the observed time points in the included studies without any increase in adverse events or complications. Epidural administration of PRP offers comparable benefit as epidural steroid injection (ESI) in the management of radiculopathy due to LDD. The safety profile of the epidural PRP is also similar to ESI.
Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy.
Vembuli H, Rajasingh S, Nabholz P … +6 more , Guenther J, Morrow BR, Taylor MM, Aghazadeh M, Sigamani V, Rajasingh J
Exp Biol Med (Maywood) · 2025 · PMID 39963344 · Full text
Bone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such...
Bone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such as limited bone availability, immune reactions, and the risk of infectious disease transmission have driven the search for alternative cell-based therapies for bone regeneration. Stem cells derived from oral tissues and umbilical cord mesenchymal stem cells (MSCs) have shown potential in both preclinical and clinical studies for bone tissue regeneration. However, their limited differentiation capacity and wound healing abilities necessitate the exploration of alternative cell sources. In this study, we generated induced pluripotent stem cells (iPSCs) using a safe, nonviral and mRNA-based approach from human periodontal ligament fibroblasts (PDLF), an easily accessible cell source. These iPSCs were subsequently differentiated into MSCs, referred to as induced MSCs (iMSCs). The resulting iMSCs were homogeneous, highly proliferative, and possessed anti-inflammatory properties, suggesting their potential as a superior alternative to traditional MSCs for regenerative therapy. These iMSCs demonstrated trilineage differentiation potential, giving rise to osteocytes, chondrocytes, and adipocytes. The iMSC-derived osteocytes (iOSTs) were homogeneous, patient-specific and showed excellent attachment and growth on commercial collagen-based membranes, highlighting their suitability for bone tissue regeneration applications. Given their promising characteristics compared to traditional MSCs, PDLF-derived iMSCs are strong candidates for future clinical studies in bone regeneration and other regenerative dental therapies.
Functional mass spectrometry indicates anti-protease and complement activity increase with COVID-19 severity.
Fraser DD, Roy S, Kuruc M … +6 more , Quintero M, Van Nynatten LR, Cepinskas G, Zheng H, Soherwardy A, Roy D
Exp Biol Med (Maywood) · 2025 · PMID 39949890 · Full text
Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly...
Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected and under constant feedback regulatory control, functional analysis is required. In this study, we used functional mass spectrometry to measure anti-protease and complement activity in plasma obtained from coronavirus disease 2019 (COVID-19) patients. Our data suggests that within 48 h of hospital admission, COVID-19 patients undergo a protease storm with significantly elevated neutrophil elastase (p < 0.001) and lymphocyte granzyme B (p < 0.01), while, anti-protease activity is significantly increased, including alpha-1 antitrypsin (AAT; p < 0.001) and alpha-1-antichymotrypsin (ACT; p < 0.001). Concurrently, the ratio of C3a to C3beta activity significantly decreased with increasing COVID-19 severity, suggesting more complement activation (Mild COVID-19 p < 0.05; Severe COVID-19 p < 0.001). Activity levels of AAT, ACT and C3a/C3beta remained unchanged over 10 hospital days. Our data suggests that COVID-19 is associated with both a protease storm and complement activation, with the former somewhat balanced with increased anti-protease activity. Evaluation of the AAT/ACT ratio and C3a/C3beta ratio indicated that COVID-19 severity is associated with both neutrophil elastase neutralization and complement activation.
Impaired fracture healing is associated with callus chondro-osseous junction abnormalities in periostin-null and osteopontin-null mice.
Teitelbaum M, Culbertson MD, Wetterstrand C … +1 more , O'Connor JP
Exp Biol Med (Maywood) · 2024 · PMID 39911634 · Full text
Periostin and osteopontin are matricellular proteins abundantly expressed in bone fracture callus. Null mutation of either the periostin () gene or the osteopontin () gene can impair bone fracture healing. However, the c...
Periostin and osteopontin are matricellular proteins abundantly expressed in bone fracture callus. Null mutation of either the periostin () gene or the osteopontin () gene can impair bone fracture healing. However, the cell and molecular pathways affected by loss of POSTN or SPP1 which lead to impaired fracture healing are not well understood. To identify potential pathways, a detailed radiological, histological, and immunohistochemical analysis of femur fracture healing in -null (KO), -null (KO), and normal (WT) mice was performed. Apparent changes in specific protein levels identified by immunohistochemistry were confirmed by mRNA quantitation. Comparisons between the KO and KO fracture calluses were confounded by interactions between the two genes; loss of reduced expression and loss of reduced expression. Consequently, alterations in fracture healing between mice heterozygous for the -null allele (HET) as well as the KO and KO mice were similar. Calluses from HET, KO, and KO mice all had dysmorphic chondro-osseous junctions and reduced numbers of osteoclasts. The dysmorphic chondro-osseous junctions in the HET, KO, and KO calluses were associated with reduced numbers of MMP-13 expressing hypertrophic chondrocytes, consistent with delayed cartilage resolution. Unlike collagen X expressing callus chondrocytes, chondrocytes only expressed MMP-13 when localized to the chondro-osseous junction or after traversing the chondro-osseous junction. Cyclooxygenase-2 (COX-2) expression also appeared to be reduced in osteoclasts from the HET, KO, and KO calluses, including in those osteoclasts localized at the chondro-osseous junction. The results indicate that POSTN and SPP1 are necessary for normal chondro-osseous junction formation and that signaling from the chondro-osseous junction, possibly from COX-2 expressing osteoclasts, regulates callus vasculogenesis and chondrocyte hypertrophy necessary for endochondral ossification during fracture healing.
Function of formyl peptide receptor 2 in adriamycin resistance of breast cancer.
Su L, Li J, Qin L … +2 more , Feng Y, Xu D
Exp Biol Med (Maywood) · 2024 · PMID 39881881 · Full text
FPRL2 has been shown to be associated with a variety of tumours but has not been well studied in breast cancer. In this study, We combine molecular biology techniques with bioinformatics to analyze the role of FPRL2 in b...
FPRL2 has been shown to be associated with a variety of tumours but has not been well studied in breast cancer. In this study, We combine molecular biology techniques with bioinformatics to analyze the role of FPRL2 in breast cancer and adriamycin resistance. By utilizing bioinformatics, we mine TCGA and GEO public databases to assess FPRL2 expression in breast cancer patients and its correlation with patient prognosis. Additionally, we employ the DepMap tool to probe the CCLE database, examining the relationship between FPRL2 gene effects and adriamycin sensitivity. Chemosensitivity of Adriamycin in breast cancer cells was tested by CCK-8 method. The apoptosis of breast cancer cells was determined by flow cytometry assay. Expression of p-ERK5 and p-AKT was determined by Western blot assay. Our results indicate that the expression level of FPRL2 in tumor tissues of breast cancer patients is significantly higher than that in normal tissues, and it correlates with poor prognosis in patients. Furthermore, the expression level of FPRL2 in tumor tissues of adriamycin-resistant breast cancer patients is also significantly higher than that in adriamycin-sensitive patients. The IC (Inhibitory Concentration 50). Of Adriamycin was significantly lower in FPRL2 silenced cells than those control cells. The apoptosis was markedly increased in FPRL2-silenced cells. p-ERK5 and p-AKT in breast cancer cells was significantly reduced after FPRL2 knocked down. In Conclusion, FPRL2 mediates Adriamycin resistance in breast cancer cells, and knockdown of FPRL2 increased apoptosis and decreased Adriamycin resistance in breast cancer cells.
Retraction: Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction - and .
EBM Editorial Office
Exp Biol Med (Maywood) · 2024 · PMID 39850546 · Full text
[This retracts the article DOI: 10.1258/ebm.2011.010361.].
[This retracts the article DOI: 10.1258/ebm.2011.010361.].
Leveraging AI to improve disease screening among American Indians: insights from the Strong Heart Study.
Rogers P, McCall T, Zhang Y … +3 more , Reese J, Wang D, Tong W
Exp Biol Med (Maywood) · 2024 · PMID 39844876 · Full text
Screening tests for disease have their performance measured through sensitivity and specificity, which inform how well the test can discriminate between those with and without the condition. Typically, high values for se...
Screening tests for disease have their performance measured through sensitivity and specificity, which inform how well the test can discriminate between those with and without the condition. Typically, high values for sensitivity and specificity are desired. These two measures of performance are unaffected by the outcome prevalence of the disease in the population. Research projects into the health of the American Indian frequently develop Machine learning algorithms as predictors of conditions in this population. In essence, these models serve as screening tests for disease. A screening test's sensitivity and specificity values, typically determined during the development of the test, inform on the performance at the population level and are not affected by the prevalence of disease. A screening test's positive predictive value (PPV) is susceptible to the prevalence of the outcome. As the number of artificial intelligence and machine learning models flourish to predict disease outcomes, it is crucial to understand if the PPV values for these methods suffer as traditional screening tests in a low prevalence outcome environment. The Strong Heart Study (SHS) is an epidemiological study of the American Indian and has been utilized in predictive models for health outcomes. We used data from the SHS focusing on the samples taken during Phases V and VI. Logistic Regression, Artificial Neural Network, and Random Forest were utilized as screening tests within the SHS group. Their sensitivity, specificity, and PPV performance were assessed with health outcomes of varying prevalence within the SHS subjects. Although sensitivity and specificity remained high in these screening tests, the PPVs' values declined as the outcome's prevalence became rare. Machine learning models used as screening tests are subject to the same drawbacks as traditional screening tests when the outcome to be predicted is of low prevalence.
Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.
Kõks S, Rallmann K, Muldmaa M … +3 more , Price J, Pfaff AL, Taba P
Exp Biol Med (Maywood) · 2024 · PMID 39844875 · Full text
Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to...
Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.
scRNA-seq reveals elevated interferon responses and TNF-α signaling via NFkB in monocytes in children with uncomplicated malaria.
Morang'a CM, Drake RS, Miao VN … +10 more , Nyakoe NK, Amuzu DSY, Appiah V, Aniweh Y, Bediako Y, Bah SY, Shalek AK, Awandare GA, Otto TD, Amenga-Etego L
Exp Biol Med (Maywood) · 2024 · PMID 39830896 · Full text
Malaria causes significant morbidity and mortality worldwide, disproportionately impacting sub-Saharan Africa. Disease phenotypes associated with infection can vary widely, from asymptomatic to life-threatening. To date...
Malaria causes significant morbidity and mortality worldwide, disproportionately impacting sub-Saharan Africa. Disease phenotypes associated with infection can vary widely, from asymptomatic to life-threatening. To date, prevention efforts, particularly those related to vaccine development, have been hindered by an incomplete understanding of which factors impact host immune responses resulting in these divergent outcomes. Here, we conducted a field study of 224 individuals to determine host-parasite factors associated with symptomatic malaria "patients" compared to asymptomatic malaria-positive "controls" at both the community and healthy facility levels. We further performed comprehensive immune profiling to obtain deeper insights into differences in response between the pair. First, we determined the relationship between host age and parasite density in patients (n = 134/224) compared to controls (n = 90/224). Then, we applied single-cell RNA sequencing to compare the immunological phenotypes of 18,176 peripheral blood mononuclear cells isolated from a subset of the participants (n = 11/224), matched on age, sex, and parasite density. Patients had higher parasite densities compared to the controls, although the levels had a negative correlation with age in both groups, suggesting that they are key indicators of disease pathogenesis. On average, patients were characterized by a higher fractional abundance of monocytes and an upregulation of innate immune responses, including those to type I and type II interferons and tumor necrosis factor-alpha signaling via NFκB. Further, in the patients, we identified more putative interactions between antigen-presenting cells and proliferating CD4 T cells, and naïve CD8 T cells driven by MHC-I and MHC-II signaling pathways, respectively. Together, these findings highlight transcriptional differences between immune cell subsets associated with disease phenotypes that may help guide the development of improved malaria vaccines and new therapeutic interventions.
Baseline gene expression in BALB/c and C57BL/6 peritoneal macrophages influences but does not dictate their functional phenotypes.
Restrepo CM, Llanes A, Herrera L … +3 more , Ellis E, Quintero I, Fernández PL
Exp Biol Med (Maywood) · 2024 · PMID 39830895 · Full text
Macrophages are effector cells of the immune system and essential modulators of immune responses. Different functional phenotypes of macrophages with specific roles in the response to stimuli have been described. The C57...
Macrophages are effector cells of the immune system and essential modulators of immune responses. Different functional phenotypes of macrophages with specific roles in the response to stimuli have been described. The C57BL/6 and BALB/c mouse strains tend to selectively display distinct macrophage activation states in response to pathogens, namely, the M1 and M2 phenotypes, respectively. Herein we used RNA-Seq and differential expression analysis to characterize the baseline gene expression pattern of unstimulated resident peritoneal macrophages from C57BL/6 and BALB/c mice. Our aim is to determine if there is a possible predisposition of these mouse strains to any activation phenotype and how this may affect the interpretation of results in studies concerning their interaction with pathogens. We found differences in basal gene expression patterns of BALB/c and C57BL/6 mice, which were further confirmed using RT-PCR for a subset of relevant genes. Despite these differences, our data suggest that baseline gene expression patterns of both mouse strains do not appear to determine by itself a specific macrophage phenotype.
Corrigendum: Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway.
Shi H, Kong R, Miao X … +7 more , Gou L, Yin X, Ding Y, Cao X, Meng Q, Gu M, Suo F
Exp Biol Med (Maywood) · 2024 · PMID 39790903 · Full text
[This corrects the article DOI: 10.1177/15353702231182214.].
[This corrects the article DOI: 10.1177/15353702231182214.].
Integrating machine learning with bioinformatics for predicting idiopathic pulmonary fibrosis prognosis: developing an individualized clinical prediction tool.
Ruan H, Ren C
Exp Biol Med (Maywood) · 2024 · PMID 39764456 · Full text
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a poor prognosis. Its non-specific clinical symptoms make accurate prediction of disease progression challenging. This study aimed to develo...
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a poor prognosis. Its non-specific clinical symptoms make accurate prediction of disease progression challenging. This study aimed to develop molecular-level prognostic models to personalize treatment strategies for IPF patients. Using transcriptome sequencing and clinical data from 176 IPF patients, we developed a Random Survival Forest (RSF) model through machine learning and bioinformatics techniques. The model demonstrated superior predictive accuracy and clinical utility, as shown by the concordance index (C-index), the area under the operating characteristic curve (AUC), Brief scores, and decision curve analysis (DCA) curves. Additionally, a novel prognostic staging system was introduced to stratify IPF patients into distinct risk groups, enabling individualized predictions. The model's performance was validated using a bleomycin-induced pulmonary fibrosis mouse model. In conclusion, this study offers a new prognostic staging system and predictive tool for IPF, providing valuable insights for treatment and management.
Circulating microRNA as promising biomarkers in hypertrophic cardiomyopathy: can advanced cardiac magnetic resonance unlock new insights in research?
Chumakova OS, Mershina EA
Exp Biol Med (Maywood) · 2024 · PMID 39744621 · Full text
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder associated with an increased risk of arrhythmias, heart failure, and sudden cardiac death. Current imaging and clinical markers are not fully sufficient in...
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder associated with an increased risk of arrhythmias, heart failure, and sudden cardiac death. Current imaging and clinical markers are not fully sufficient in accurate diagnosis and patient risk stratification. Although known cardiac biomarkers in blood are used, they lack specificity for HCM and primarily stratify for death due to heart failure in overt cases. Non-coding RNAs, particularly microRNAs, have emerged as promising biomarkers due to their role in regulating gene expression in both healthy and pathological hearts. Circulating microRNA signatures may dynamically reflect the progression of HCM, offering potential utility in diagnosis and disease monitoring as well as inform biologic pathways for innovative therapeutic strategies. However, studying microRNAs in cardiovascular diseases is still in its early stages and poses many challenges. This review focuses on emerging research perspectives using advanced cardiac magnetic resonance techniques. We presume, that the search for circulating miR signatures associated with specific adverse myocardial features observed on cardiac magnetic resonance imaging - such as fibrosis, disarray, and microvascular disease - represents a promising direction in HCM research.
Berberine alleviates AGEs-induced ferroptosis by activating NRF2 in the skin of diabetic mice.
Jiang C, Lao G, Ran J … +1 more , Zhu P
Exp Biol Med (Maywood) · 2024 · PMID 39735782 · Full text
Advanced glycation end products (AGEs) have adverse effects on the development of diabetic complications. Berberine (BBR), a natural alkaloid, has demonstrated its ability to promote the delayed healing of skin wounds. H...
Advanced glycation end products (AGEs) have adverse effects on the development of diabetic complications. Berberine (BBR), a natural alkaloid, has demonstrated its ability to promote the delayed healing of skin wounds. However, the impact of BBR on AGEs-induced ferroptosis in skin cells and the underlying molecular mechanisms remains unexplored. This study investigated the involvement of ferroptosis in AGEs-induced keratinocyte death, and the impact of BBR on ferroptosis in a db/db mouse model with long-term hyperglycemia was elucidated. A remarkable reduction in cell viability was observed along with increased malondialdehyde (MDA) production in AGEs-induced HaCaT cells. Intracellular reactive oxygen species (ROS) and iron levels were elevated in cells exposed to AGEs. Meanwhile, the protein expression of glutathione peroxidase 4 (GPX4) and ferritin light chain (FTL) was significantly decreased in AGEs-treated cells. However, pretreatment with BBR markedly protected cell viability and inhibited MDA levels, attenuating the intracellular ROS and iron levels and increased expression of GPX4 and FTL . Significantly diminished antiferroptotic effects of BBR on AGEs-treated keratinocytes were observed upon the knockdown of the nuclear factor E2-related factor 2 () gene. , GPX4, FTL, and FTH expression in the epidermis of diabetic mice was significantly reduced, accompanied by enhanced lipid peroxidation. Treatment with BBR effectively rescued lipid peroxidation accumulation and upregulated GPX4, FTL, FTH, and NRF2 levels in diabetic skin. Collectively, the findings indicate that ferroptosis may play a significant role in AGEs-induced keratinocyte death. BBR protects diabetic keratinocytes against ferroptosis, partly by activating NRF2.
Increased hip fracture risk in the patients with type 2 diabetes mellitus is correlated with urine albumin-to-creatinine ratio (ACR) and diabetes duration in men.
Ding H, Wang H, Liu G … +4 more , Wang Y, Han D, Zhang X, Song L
Exp Biol Med (Maywood) · 2024 · PMID 39735781 · Full text
Patients with type 2 diabetes mellitus (T2DM) have increased hip fracture risk. And the association between urine albumin to creatinine ratio (ACR) and an increased risk of hip fracture in patients with T2DM remains cont...
Patients with type 2 diabetes mellitus (T2DM) have increased hip fracture risk. And the association between urine albumin to creatinine ratio (ACR) and an increased risk of hip fracture in patients with T2DM remains controversial. This study aimed to investigate the association between urinary ACR and hip fracture risk in postmenopausal women and aged men with T2DM. The study included 219 postmenopausal women and 216 older men (mean age >60 years) with T2DM. Women and men were divided into control group (ACR<30 mg/g), microalbuminuria group (30 mg/g ≤ ACR<300 mg/g), and macroalbuminuria group (ACR≥300 mg/g) respectively. Demographic characteristics and clinical history were collected in patients. Biochemical indexes and bone turnover-related markers were measured in patients. In the study, we found that several factors, including age, T2DM duration, cerebral infarction history, serum corrected calcium levels and urine ACR were positively associated with hip fracture risk. However, 25-Hydroxyvitamin D and areal BMD were negatively associated with hip fracture risk. Furthermore, multiple regression analysis showed that urinary ACR level (β = 0.003, p = 0.044) and duration of T2DM (β = 0.015, p = 0.018) were positively and independently correlated with hip fracture risk in older men. In contrast, femoral neck BMD (β = -6.765, p < 0.001) was independently and negatively correlated with hip fracture risk in older men. This study indicated that the elevated ACR levels and longer T2DM duration were related to higher hip fracture risk in older men with T2DM, which could be beneficial for developing a predictive model for osteoporotic fractures in patients with type 2 diabetes in the future. However, results were inconsistent in women, hip fracture risk didn't alter by changes in urinary microalbuminuria level in postmenopausal women with T2DM.
Dysregulated transfer RNA-derived small RNAs as potential gastric cancer biomarkers.
Yuan J, Gu W, Xu T … +7 more , Zhang Y, Shen L, Yan J, Guan X, Chu H, Yuan R, Ju S
Exp Biol Med (Maywood) · 2024 · PMID 39735780 · Full text
Gastric cancer (GC) is the kind of carcinoma that has the highest rates of morbidity and death worldwide. In the early stages of GC, there is currently an absence of sensitive and specific biomarkers. The newly-discovere...
Gastric cancer (GC) is the kind of carcinoma that has the highest rates of morbidity and death worldwide. In the early stages of GC, there is currently an absence of sensitive and specific biomarkers. The newly-discovered class of non-coding RNAs (ncRNAs) known as transfer RNA-derived small RNAs (tsRNAs) is highly expressed in bodily fluids and neoplastic cells. High-throughput sequencing was initially employed to identify differentially expressed tsRNAs in early GC patients, followed by validation in patient serum, GC tissues, and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We identified dysregulated tsRNAs (the up-regulated tsRNAs included tRF-31-PNR8YP9LON4VD, tRF-30-MIF91SS2P4FI, and tRF-30-IK9NJ4S2I7L7, whereas the down-regulated tsRNAs included tRF-38-W6RM7KYUPRENRHD2, tRF-37-LBRY73W0K5KKOV2, tRF-36-JB59V3WD8YQ84VD, tRF-25-MBQ4NKKQBR, and tRF-36-0KFMNKYUHRF867D) in GC, and we verified that the serum of patients, GC cells and tissues both consistently expressed these tsRNAs. Additionally, GC patients' serum had considerably greater expression levels of the three up-regulated tsRNAs than did healthy controls. Receiver operating characteristic (ROC) curve analysis demonstrated that the sensitivity and specificity of the three up-regulated tsRNAs were superior to those of CEA, CA199, and CA724 in the process of diagnosing GC, particularly in its early stages. This suggests that tsRNAs have great diagnostic efficacy and potential as new "liquid biopsy" biomarkers for the diagnosis of GC. Using bioinformatics software, we predicted that dysregulation of tsRNAs may be a potential regulatory mechanism for the development of GC.
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