Tag: pubmed

Stem Cell Rev Rep. 2025 Jun 28. doi: 10.1007/s12015-025-10929-1. Online ahead of print.

ABSTRACT

BACKGROUND: The limited regenerative capacity of epidermal cells following tissue injury impairs wound healing in diabetic foot ulcers (DFUs), contributing to elevated rates of amputation and mortality. Recent advances have demonstrated that somatic cells can be reprogrammed into diverse cell types through the application of defined reprogramming factors. This study aims to develop a safe, efficient, and clinically translatable strategy for skin regeneration via direct lineage reprogramming.

METHODS: We established a novel reprogramming approach using a combination of two factors, BMI1 and FGFR2b (termed B2), to induce fibroblast-to-keratinocyte-like cells (iKCs) conversion in vitro and delivered via adeno-associated virus 9 (AAV9) in vivo. Molecular and functional characteristics of iKCs were evaluated by qRT-PCR, Western blot, immunofluorescence, transcriptomic analysis, and in vitro differentiation assays. A diabetic (db/db) mouse skin wound model was used to assess the regenerative potential and therapeutic effects. Statistical significance was determined using Student’s t-test or one-way ANOVA.

RESULTS: iKCs-B2 (Keratinocyte-like cells form from B2-infected L929) exhibited both morphological and functional characteristics comparable to primary keratinocytes. In vivo, AAV9-mediated delivery of B2 factors significantly promoted wound closure, reconstructed stratified epithelium, restored barrier function, and markedly reduced the mortality rate.

CONCLUSIONS: This study presents a safe and effective direct reprogramming strategy for skin regeneration, bypassing the pluripotent stage and avoiding cell transplantation. The B2 combination provides a novel molecular tool for wound repair and offers translational potential for treating non-healing wounds such as DFUs.

PMID:40579673 | DOI:10.1007/s12015-025-10929-1

Geroscience. 2025 Jun 27. doi: 10.1007/s11357-025-01777-5. Online ahead of print.

ABSTRACT

Dysregulation of lipid metabolism is increasingly recognized as a key factor in the pathogenesis of Alzheimer’s disease (AD). Unfortunately, an accurate lipidomic fingerprints in AD patients’ biofluids remains challenging. A comprehensive analysis of plasma samples from 26 patients with AD and 30 healthy individuals was performed using untargeted and targeted lipidomics techniques with strict lipid annotation criteria. By monitoring characteristic fragments per precursor, we achieved precise lipid characterization and quantification for approximately 270 lipid species. Multivariate statistical analysis revealed a distinct lipid profile between AD patients and controls, with 72 lipids significantly altered (FC > 1.5 or < 0.667, VIP > 1, P < 0.05). Notably, a biomarker analysis based on the multivariate exploratory receiver operating characteristic (ROC) curve identified a comprehensive panel consisting of 10 novel lipids as potential markers for AD, achieving 98.2% accuracy with a favorable auxiliary diagnostic value (area under curve of 0.995). Additionally, the higher levels of SM(d18:1/16:0), SM(d18:1/18:1), and LPE 18:0 were strongly correlated with the clinical dementia rating (CDR) and mini-mental state examination (MMSE) scores, underscoring the therapeutic potential of lipid modulation in AD. These findings reveal the intricate relationship between lipid alterations and AD pathology and emphasize the necessity for LC-MRM/MS lipidomics with rigorous criteria in the discovery of reliable biomarkers, enriching our understanding of lipid roles in neurodegenerative processes and informing future mechanistic investigations and drug target development.

PMID:40579668 | DOI:10.1007/s11357-025-01777-5

World J Pediatr. 2025 Jun 27. doi: 10.1007/s12519-025-00932-4. Online ahead of print.

ABSTRACT

BACKGROUND: The risk-benefit balance and safety of postnatal corticosteroid use for chronic lung disease (PNCSCLD) in preterm infants is a controversial matter. Our objective was to determine the trends in the use of PNCSCLD over eleven years and to analyze the neurodevelopmental consequences of PNCSCLD in preterm infants at 18-42 months of corrected age.

METHODS: The data for this retrospective population-based cohort study were obtained from ten tertiary neonatal intensive care units across New South Wales and the Australian Capital Territory, Australia. Preterm infants < 29⁺⁰ weeks’ gestation born between January 1, 2007, and December 31, 2017, who were alive at discharge, without any major congenital anomalies were included and analyzed based on their PNCSCLD status.

RESULTS: Over eleven years, 611 (14.3%) out of 4258 infants received PNCSCLD. Among the 3386 eligible infants, 2636 (77.8%) underwent neurodevelopmental follow-up and were included in the final analysis. The rate of PNCSCLD use increased from 12.4% in 2007 to 19.6% in 2017. Similarly, the rate of moderate to severe functional disability (MSFD) increased from 8.8% in 2007 to 16.1% in 2017. Propensity-adjusted analysis revealed a greater odds ratio (OR) for MSFD in the PNCSCLD group than in the control group [average treatment effect: OR = 1.252, 95% confidence interval (CI) = 1.185-1.322, P ≤ 0.001; average treatment effect on the treated group: OR = 1.104, 95% CI = 1.031-1.184, P = 0.005].

CONCLUSIONS: PNCSCLD use was associated with a greater incidence of MSFD. Clinicians should exercise caution when using PNCSCLD.

PMID:40579659 | DOI:10.1007/s12519-025-00932-4

Diabetologia. 2025 Jun 27. doi: 10.1007/s00125-025-06473-9. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Excess type 2 diabetes mellitus in minority ethnic groups remains unexplained, although greater fat mass makes a strong contribution. We hypothesised that height and weight through infancy in South Asian and Black African/Caribbean subgroups is more adverse than in White populations. These, allied to poor socioeconomic position, determine greater fat mass at age 7 years.

METHODS: We report a secondary analysis from the UK Millennium Cohort Study, including 12,280 births of White ethnicity, and 358 of Indian, 650 of Pakistani, 268 of Bangladeshi, 163 of Black Caribbean and 277 of Black African ethnicity between 2000 and 2002. Birthweight was reported, and heights and weights were measured at ages 3, 5, 7, 11, 14 and 17 years. Bioimpedance captured fat mass, indexed to height, at ages 7, 11, 14 and 17 years. Standardised differences in anthropometry, using the White group as the comparator, were calculated. We explored the effect of early growth on ethnic differences in fat-mass index at age 7 years. Confounders included maternal anthropometry, smoking, infant breastfeeding, education, parental income and area-level socioeconomic deprivation.

RESULTS: All minority ethnic subgroups had lower birthweight and accelerated infant height and weight growth compared with White children. By age 3 years, mean height was greater in all minority ethnic groups than in White children. This height advantage was progressively lost, first in Bangladeshi children. By age 17 years in boys/girls, Indians were 1.77/2.48 cm, Pakistanis 2.24/3.44 cm, Bangladeshis 4.83/5.95 cm and Black Caribbeans 1.64/0.49 cm shorter than White children. Heights were equivalent in Black African children. By age 17 years, all South Asian children were lighter, and Black African/Caribbean children heavier, than White children. The anthropometric gradient by ethnicity in children mirrored that in mothers. Girls from minority ethnic groups were more likely to be menstruating by age 11 years than White girls (range 12-27% vs 9%). At age 7 years, standardised fat-mass index (kg/m²) in boys/girls was 0.17/0.01 SDs greater in Indian, 0.21/0.04 in Pakistani, 0.18/0.16 in Bangladeshi, 0.48/0.35 in Black Caribbean and 0.37/0.75 in Black African children than in White children. These differences persisted to age 17 years. Weight gain to age 3 years, and in Black Africans/Caribbeans, adverse individual and neighbourhood socioeconomic position, contributed to ethnic differences in fat mass.

CONCLUSIONS/INTERPRETATION: Minority ethnic groups in the UK have poorer childhood growth than White children, achieving shorter height, greater fat mass and earlier female puberty. Mirroring of maternal and offspring ethnic subgroup gradients in height and weight indicates intergenerational transmission. Persistent adverse socioeconomic circumstances perpetuate ethnic adversity in early life accrual of body fat.

DATA AVAILABILITY: All MCS data used in this analysis are available from UK Data Service with an end user licence ( https://ukdataservice.ac.uk/find-data/ ).

PMID:40579638 | DOI:10.1007/s00125-025-06473-9

J Racial Ethn Health Disparities. 2025 Jun 27. doi: 10.1007/s40615-025-02523-5. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess providers’ substance use screening/testing practices in patient care and identify disparities in their application. We hypothesized that patient race and social vulnerability (SV) are independently and jointly associated with increased rates of provider self-reported substance use screening/testing.

METHODS: A 2 × 2 factorial vignette design was used to survey OB/GYN, Midwifery, and Family Medicine providers. The patients’ age and medical characteristics were identical in each vignette, but two elements varied dichotomously: (1) the patient’s race (Black vs. White) and (2) the patient’s level of SV. Descriptive statistics were computed to assess respondent characteristics. Chi-square or Fisher’s exact tests were performed to assess disparities in substance use screening/testing practices.

RESULTS: Providers shown the SV patient vignette, compared to providers shown the vignette for a non-SV patient, reported that the patient’s housing (41% vs. 10%, p < 0.01), substance use history (97% vs. 67%, p < 0.01), and the number of prenatal care visits (59% vs. 27%, p = 0.02) influenced their decision to screen/test the patient for substance use. Providers shown the vignette for the SV Black patient were more likely to report the patient’s housing (47% vs. 6%, p = 0.04), substance use history (93% vs. 56%, p = 0.01), and gestational age (20% vs. 0%, p = 0.03) influenced their screening/testing recommendations.

CONCLUSION: Providers reported that the patient’s level of SV influenced their decision to recommend screening/testing. The combination of race and SV had the largest impact on reported decisions regarding screening/testing practices. The results of this study highlight the need for standardized institutional substance use detection protocols to reduce provider bias and discrimination in substance use screening/testing based on individual patient demographics.

PMID:40579635 | DOI:10.1007/s40615-025-02523-5

J Racial Ethn Health Disparities. 2025 Jun 27. doi: 10.1007/s40615-025-02490-x. Online ahead of print.

ABSTRACT

BACKGROUND: Racial disparities in surgical outcomes are well documented across various procedures, including oncological and reconstructive breast surgery. However, it remains unclear whether these inequalities extend to reduction mammoplasty.

METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database between 2011 and 2022 to identify adult female patients who underwent breast reduction and reported their racial identity. 30-day postoperative outcomes were compared across four racial groups-Asian, Black/African American, American Indian/Alaskan Native, and Native Hawaiian/Pacific Islander-against White patients using univariate and confounder-adjusted multivariate analyses.

RESULTS: The study cohort included 26,329 female patients, with 64% (n = 16,930) identified as White, 34% (n = 8,873) as Black/African American, 1.2% (n = 326) as Asian, 0.41% (n = 109) as American Indian/Alaska Native, and 0.35% (n = 91) as Native Hawaiian/Pacific Islander. A total of 1,660 adverse events (6.3%) occurred, with complication rates ranging from 4.0% (n = 13) in Asian patients to 6.5% (n = 1,108) in White patients. While breast reduction surgery was generally safe across all racial groups, multivariable analysis identified subtle yet statistically significant disparities: Black/African American patients had a significantly lower likelihood of overall (OR = 0.81) and surgical complications (OR = 0.65), including superficial incisional infections (OR = 0.50; all p < 0.001), but a higher risk of deep incisional infections (OR = 1.4; p = 0.013) and unplanned readmissions (OR = 1.3; p < 0.001). Asian patients demonstrated a significantly lower risk of surgical complications (OR = 0.23; p = 0.041).

CONCLUSION: Breast reduction surgery is generally safe across all racial groups; however, our findings also unveiled subtle racial disparities in its postoperative outcomes. Black/African American patients were found to have a lower risk of overall and surgical complications but were more susceptible to deep incisional infections and unplanned readmissions. Asians were significantly less likely to experience surgical complications. These results reinforce the strong safety profile of reduction mammoplasty while underscoring the need for further research into the underlying factors contributing to differential outcomes.

PMID:40579632 | DOI:10.1007/s40615-025-02490-x

Theor Appl Genet. 2025 Jun 27;138(7):163. doi: 10.1007/s00122-025-04948-2.

ABSTRACT

Multi-omics assisted prediction of disease resistance mechanisms using machine learning has the potential to accelerate the breeding of resistant legume varieties. Grain legumes, such as soybean (Glycine max (L.) Merr.), chickpea (Cicer arietinum L.), and lentil (Lens culinaris Medik.) play an important role in combating micronutrient malnutrition in the growing human population. However, plant diseases significantly reduce grain yield, causing 10-40% losses in major food crops. The genetic mechanisms associated with disease resistance in legumes have been widely studied using genomic approaches. Multi-omics data encompassing various biological layers such as the transcriptome, epigenome, proteome, and metabolome, in addition to the genome, enables researchers to gain a deeper understanding of these complementary layers and their roles in complex legume-pathogen interactions. Genomic prediction, used to select the best genotypes with desirable traits for breeding, has largely relied on genome-wide markers and statistical approaches to estimate the breeding values of individuals. Integrating multi-omics data into genomic prediction can be achieved using machine learning models, which can capture nonlinear relationships prevalent in high-dimensional data better than traditional statistical methods. This integration may enable more accurate predictions and identification of resistance mechanisms for breeding resistant legumes. Despite its potential, multi-omics integration for disease resistance prediction in legumes has been largely unexplored. In this review, we explore omics studies focusing on disease resistance in legumes and discuss how machine learning models can integrate multi-omics data for disease resistance prediction. Such multi-omics assisted prediction has the potential to reduce the breeding cycle for developing disease-resistant legume varieties.

PMID:40579624 | DOI:10.1007/s00122-025-04948-2

Eur J Orthop Surg Traumatol. 2025 Jun 27;35(1):284. doi: 10.1007/s00590-025-04392-4.

ABSTRACT

PURPOSE: To describe nonunion and fracture-related infection (FRI) rates and patient-reported outcomes following operative treatment for distal femur fractures in young patients.

METHODS: We retrospectively identified all patients (aged 18-50) who were operatively treated for a distal femur fracture between 2006 and 2023 with ≥ 3-month clinical follow-up at two Level 1 Trauma Centers. Outcomes included reoperation for nonunion and FRI; and PROMIS physical function (PF), depression, and anxiety (reference population mean: 50). Multiple linear regression was performed to identify factors associated with PROMIS-PF.

RESULTS: Eighty-six patients met inclusion criteria. The median age was 34 years, 71% were male, 42% had an open fracture, and for 38 patients PROMIS scores were collected at an average of 9.8 years after treatment. Eleven patients (13%) required reoperation for nonunion and 3 (3.5%) for FRI. Median PROMIS-PF was 47.0 (IQR: 41.2-52.4), depression 45.8 (IQR: 38.9-53.6), and anxiety 46.7 (IQR: 39.5-60.5). PROMIS-PF was lower than the reference population score (p < 0.05). Increased age (1-year; ß: – 0.39; 95%CI: – 0.62 to – 0.17; p < 0.001) and BMI (1-unit; ß: – 0.59; 95%CI: – 0.98 to – 0.20; p = 0.004) at time of injury were associated with worse PROMIS-PF scores and longer follow-up (1-year; ß: 0.79; 95% CI: 0.27 to 1.3; p = 0.004) with better scores.

CONCLUSION: One in 8 young patients with a distal femur fracture underwent reoperation for nonunion and one in 33 for FRI. Physical function scores were marginally lower than the reference population, whereas depression and anxiety scores were similar. The finding that physical function scores were more influenced by baseline patient factors than injury characteristics is important for prognostication and patient education. These results should be interpreted in the context of the small sample size, and future research with larger cohorts is needed to confirm these findings and better understand long-term functional outcomes in young patients following treatment of distal femur fractures.

PMID:40579623 | DOI:10.1007/s00590-025-04392-4

AAPS J. 2025 Jun 27;27(5):115. doi: 10.1208/s12248-025-01102-0.

ABSTRACT

In vitro dissolution testing is commonly performed to ensure that oral solid dosage medicines are of high quality and will achieve their targeted in vivo performance. However, this testing is time and material consuming. Therefore, pharmaceutical companies have been developing predictive dissolution models (PDMs) for drug product release based on fast at- and/or on-line measurements, including real-time release testing of dissolution (RTRT-D). Recently, PDMs have seen acceptance by major regulatory bodies as release tests for the dissolution critical quality attribute. In this paper, several methodologies are described to develop and validate a fit-for-purpose model, then to implement it as a surrogate release test for dissolution. These approaches are further exemplified by real-life case studies, which demonstrate that PDMs for release are not only viable but more sustainable than in vitro dissolution testing and can significantly accelerate drug product release. The rise of continuous manufacturing within the pharmaceutical industry further favors the implementation of real-time release testing. Therefore, a steep uptake of PDMs for release is expected once this methodology is globally accepted. To that end, it is advantageous for global regulators and pharmaceutical innovators to coalesce around a harmonized set of expectations for development, validation, implementation, and lifecycle of PDMs as part of drug product release testing.

PMID:40579614 | DOI:10.1208/s12248-025-01102-0

AAPS PharmSciTech. 2025 Jun 27;26(6):174. doi: 10.1208/s12249-025-03163-y.

ABSTRACT

Breast cancer (BC) is the most prevalent form of cancer among women worldwide, accounting for approximately 36% of cancer cases. Due to its inimitable pathological expression and restricted success of accessible therapeutic modalities, fanatical research in this area is essential. Our group has developed a nanovesicular lipid carrier system consisting of Exemestane (EXM) and Genistein (GNS), which have been successfully incorporated into both uncoated and chitosan-coated liposomes. This combination aims to enhance anticancer efficacy. EXM is known to cause bone loss, while GNS, a natural isoflavone, has been shown in research to possess bone-protective effects. Therefore, we combined these two compounds to mitigate the side effects of EXM. Our previous publication details the formulation development of uncoated EXM-GNS liposomes (EXM-GNS-LPS) and chitosan-coated EXM-GNS liposomes (CH-EXM-GNS-LPS), where we addressed the pharmacotechnical challenges of combining a synthetic drug with herbal drug. Both uncoated and coated liposomes were tested for their budding effects on bone loss induced by hormonal therapy. Pharmacokinetic and pharmacodynamic studies were conducted on rat models with breast cancer, treated with different formulations. Biochemical investigations revealed significant changes in biomarker levels, indicating effects on bone development and resorption. Improvements in bone health and anticancer efficacy were observed to be statistically significant (p < 0.05). Micro-CT analysis of bone samples showed that the chitosan-coated EXM-GNS liposome treatment group yielded the best results when evaluate against other treatment groups. Additionally, histological examination of the bone treated with CH-EXM-GNS-LPS demonstrated a marked restoration of trabecular bone architecture, characterized by a well-connected bone matrix and narrower inter-trabecular spaces compared to the toxic control group. The synergistic effect of EXM and GNS, encapsulated in liposomes, offers an innovative solution to the challenges of breast cancer treatment. The chitosan coating not only improved the stability and controlled release of the drugs but also provided additional benefits in terms of biocompatibility and targeting potential. Overall, the results of this study indicate that the CH-EXM-GNS-LPS formulation holds significant promise as a therapeutic and preventive strategy for bone loss associated with hormonal therapy in breast cancer patients. This work lays the foundation for future clinical applications, highlighting the potential for combining synthetic and natural compounds in advanced drug delivery systems to address complex, multifactorial health issues.

PMID:40579610 | DOI:10.1208/s12249-025-03163-y