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Dendritic cell-derived MYD88 potentiates as a biomarker for immune regulation in hepatocellular carcinoma and may predict a better immunological result

Front Cell Dev Biol. 2025 Mar 24;13:1554705. doi: 10.3389/fcell.2025.1554705. eCollection 2025.

ABSTRACT

INTRODUCTION: MYD88 (myeloid differentiation primary response 88) is a key adaptor protein mediate immune responses, primarily through Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) signaling. The TLR/MYD88 pathway plays a critical role in dendritic cells (DC) maturation and function, contributing to the body’s innate immunity. Recent studies have further highlighted MYD88’s pivotal role in intrinsic immunity and its regulatory influence on the tumor microenvironment (TME) in hepatocellular carcinoma (HCC). The expression of MYD88 in DCs and its regulatory role in the TME have gained increasing attention.

METHODS: RNA-sequencing data retrieved from the TCGA and GEO databases were utilized for both the training and validation of our signature. Single-cell RNA transcriptome data from GEO were analyzed to investigate the correlation among subclusters of T cells, myeloid cells, and dendritic cells (DCs) within the HCC tumor microenvironment (TME). A combination of bioinformatics and machine learning approaches was employed to perform statistical analyses.Additionally, flow cytometry was conducted to quantify T cell subtypes and assess biomarker expression in DCs. A BALB/c-derived xenograft mouse model was established to evaluate the functional role of MyD88 in tumor progression and immunotherapy response. Furthermore, immunohistochemical (IHC) staining was performed to reassess the biological effects of MyD88 in HCC patients undergoing immune checkpoint inhibitor (ICI) therapy.

RESULTS: Our pan-cancer data analysis further highlights the significant impact of MYD88 on clinical outcomes in HCC. Analysis of TCGA and GEO databases confirms that MYD88 serves as a key signaling molecule in DCs, reinforcing its critical role in immune regulation. Our in vitro experiments demonstrates that MyD88 modulates T cell function through DCs. In vivo, H22 tumor cells exhibited accelerated growth in MyD88 knockout mice and a reduced response to anti-PD-1 treatment, whereas wild-type mice showed the opposite trend.

DISCUSSION: These findings underscore the critical role of MYD88 in DC function, suggesting its potential as a biomarker for immunoregulation in HCC. By shaping the TME, MYD88 not only regulates the immune response in HCC but also influences patient clinical outcomes. Both ex vivo and in vivo experiments further validate that MYD88 impacts DC functionality, contributing to variations in HCC progression.

PMID:40196847 | PMC:PMC11973264 | DOI:10.3389/fcell.2025.1554705

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Cell protective effects of vitamin C against oxidative stress induced by ciprofloxacin on spermatogenesis: involvement of cellular apoptosis

Front Cell Dev Biol. 2025 Mar 20;13:1489959. doi: 10.3389/fcell.2025.1489959. eCollection 2025.

ABSTRACT

INTRODUCTION: Ciprofloxacin (CPFX), a second-generation fluoroquinolone, is widely used as an anti-infective agent for genitourinary tract infections due to its broad-spectrum efficacy against gram-positive and gram-negative organisms. Although CPFX is considered safe at therapeutic doses, recent evidence suggests its potential biological toxicity, particularly affecting testicular histology and function. This study aimed to investigate the effects of CPFX on testicular structure and function and to evaluate the protective role of vitamin C.

METHODS: Forty adult male albino rats were divided into four groups: control, CPFX-treated, vitamin C-treated, and CPFX combined with vitamin C-treated. After 60 days of treatment, blood samples were collected for hormonal assays, while testicular and epididymal tissues were analyzed using light and electron microscopy. Oxidative stress markers, including malondialdehyde (MDA), glutathione (GSH), and catalase (CAT) enzyme activity, were assessed. Statistical analyses were conducted using SPSS software.

RESULTS: Confocal microscopy of the CPFX-treated group revealed significant reductions in germ cell populations within seminiferous tubules, accompanied by severe apoptosis and degenerative epithelial changes. Morphometric analysis confirmed a decrease in tubular diameter and epithelial height, degeneration of spermatogenic cells, and detachment of apoptotic cells from the basement membrane. CPFX treatment significantly reduced testosterone levels and induced variable changes in gonadotropin hormones (LH and FSH). Co-administration of vitamin C with CPFX restored normal testicular morphology, preserving seminiferous tubule integrity and maintaining spermatogenic cell populations and spermatozoa within the lumen.

DISCUSSION AND CONCLUSION: Vitamin C supplementation effectively mitigated CPFX-induced oxidative stress by significantly reducing MDA levels and enhancing antioxidant defenses, including increased GSH content and CAT enzyme activity. These findings highlight the therapeutic potential of vitamin C in reversing CPFX-induced testicular toxicity by alleviating oxidative stress and restoring testicular function.

PMID:40196846 | PMC:PMC11973441 | DOI:10.3389/fcell.2025.1489959

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Co-cultivation effects of Lactobacillus plantarum and Pichia pastoris on the key aroma components and non-volatile metabolites in fermented jujube juice

RSC Adv. 2025 Apr 7;15(14):10653-10662. doi: 10.1039/d5ra00193e. eCollection 2025 Apr 4.

ABSTRACT

Fermented jujube products are gradually becoming popular. However, few studies have focused on the relationship between the metabolites and aroma compounds in jujube during the fermentation process. Hence, in this study, jujube was fermented with the co-culture of Lactobacillus plantarum and Pichia pastoris, and the key volatile organic components (VOCs) and non-volatile organic components (nVOCs) in the fermented jujube juice (FJJ) were studied to determine the possible aromatic production pathway during microbial metabolism and propose the possibility of regulating flavor during fermentation. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to analyze and compare the VOCs in the jujube juice before and after fermentation, which showed that the fermented aroma had increased floral, winy and sour notes. Specifically, 13 key aroma compounds were found using the aroma extract dilution analysis (AEDA) and aroma recombination/omission model. Additionally, 32 differential nVOC metabolites, mainly involved in amino acid and nucleotide metabolism pathways, were screened in FJJ using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate statistical analysis. After correlation analysis, 14 nVOCs were significantly correlated with 8 key aroma compounds. This study indicates that the combination of Lactobacillus plantarum and Pichia pastoris may supply a new mixed fermentation agent towards fermented jujube products and provides reference values for flavor regulation in the co-fermentation of jujube juice.

PMID:40196838 | PMC:PMC11973478 | DOI:10.1039/d5ra00193e

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A randomised, parallel-group clinical trial comparing bedinvetmab to meloxicam for the management of canine osteoarthritis

Front Vet Sci. 2025 Mar 24;12:1502218. doi: 10.3389/fvets.2025.1502218. eCollection 2025.

ABSTRACT

Bedinvetmab (Librela®), a fully canine anti-nerve growth factor monoclonal antibody, was compared to the non-steroidal anti-inflammatory drug (NSAID) meloxicam in dogs for the management of osteoarthritis-related pain in a randomised, open-label, multicentre, parallel-group study. Subjects were recruited from general practices as client-owned dogs with appendicular osteoarthritis. Dogs were block randomised 1:1 to either daily oral meloxicam or bedinvetmab, administered subcutaneously once a month. The primary endpoint for efficacy was the change from baseline in the Canine Orthopaedic Index (COI) score. Linear mixed-effects models were used for statistical analysis conducted on a per-protocol and intent-to-treat basis. We hypothesised that bedinvetmab would demonstrate superior efficacy and safety compared to meloxicam; the number needed to harm (NNH) for meloxicam, relative to bedinvetmab, was calculated. Of the 190 screened dogs, 101 were randomised (bedinvetmab 52; meloxicam 49). Overall, both treatment groups showed a significant reduction in COI scores relative to baseline (p < 0.001). The bedinvetmab group experienced a larger mean reduction in COI scores, but this was not statistically significant. A significant effect of the visit was observed, with later visits showing a significantly greater reduction in COI compared to Visit 2 (p < 0.001). The bedinvetmab group reported four (AEs), whilst the meloxicam group reported 17, with nine of those being gastrointestinal system disorders. Additionally, more dogs in the bedinvetmab group completed the study (n = 44) compared to those in the meloxicam group (n = 33). This is the first study to compare bedinvetmab to an NSAID for the management of osteoarthritis-related pain in dogs. The results suggest that both products are equally effective in managing OA pain, with efficacy improving over time for both treatments. Bedinvetmab was associated with fewer AEs. These data will aid clinicians and pet owners in choosing analgesic options for dogs with osteoarthritis.

PMID:40196808 | PMC:PMC11974340 | DOI:10.3389/fvets.2025.1502218

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Surface N- or O-linked glycans on bovine spermatozoa play minimal role in evading macrophage mediated phagocytosis

Front Vet Sci. 2025 Mar 24;12:1550100. doi: 10.3389/fvets.2025.1550100. eCollection 2025.

ABSTRACT

Bull spermatozoa possess glycocalyx made of carbohydrate moieties attached to proteins and lipids on their membranes that is involved in fertility associated functions including immune evasion in the female reproductive tract. The current study aimed to establish whether the differences in the glycocalyx of spermatozoa provide selective advantage in evading phagocytosis mediated by female macrophages. Based on removal of either N- or O-linked surface glycans from the spermatozoa, their susceptibility to phagocytosis by macrophages was assessed in vitro in bovines (Bos indicus) through flow cytometry. We found no significant difference (p > 0.05) in the phagocytosis of spermatozoa without N-glycans or O-glycans compared to those with intact glycocalyx. Out of nearly 2,000 events analysed, the mean number of macrophages phagocytosing the spermatozoa were found to be 416, 423 and 345, respectively for spermatozoa with an intact glycocalyx, with N-glycans removed and with O-glycans removed. The difference in the mean values of the individual sample geometric mean fluorescence intensities (n = 3) of the phagocytosed spermatozoa among all the treatment groups were also statistically insignificant (p > 0.05) indicating that the macrophages are not involved in the selection of spermatozoa based on their surface glycan profiles. Therefore, it is plausible to conclude that macrophages may be exploiting other signature molecules if at all they are involved in the cryptic female choice, or they might be phagocytosing spermatozoa with less stringency that may not be dependent on O- or-N-glycans on sperm surface. However, further studies are required to gain deeper insights into this phenomenon.

PMID:40196804 | PMC:PMC11973392 | DOI:10.3389/fvets.2025.1550100

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Disease Activity in Rheumatoid Arthritis Patients Stratified by Hemoglobin Levels: A Multi-center Study

Oman Med J. 2024 Sep 30;39(5):e671. doi: 10.5001/omj.2024.101. eCollection 2024 Sep.

ABSTRACT

OBJECTIVES: Hemoglobin (Hb) level and its relation to rheumatoid arthritis (RA) is multifactorial. The primary aim of this study was to examine the association between Hb levels and disease activity in patients with RA.

METHODS: This retrospective study obtained data from adult RA patients with Hb reports from the Kuwait Registry for Rheumatic Diseases. Patients were recruited from four public hospitals in Kuwait between February 2013 and February 2022. The cohort was stratified into two groups: Hb ≤ 110 g/L and Hb > 110 g/L. Demographic, treatment, clinical, and laboratory characteristics were used to compare the two Hb groups. Multivariate and univariate statistical analyses were used to analyze the data.

RESULTS: The total number of patients visited (Nv) was 11 393 and consecutive patients with RA diagnoses and Hb data (Np) were 1584. Both Nv and Np were included in the study. Of these, 72.5% (n = 8260) had high Hb levels and 27.5% (n = 3133) had low Hb levels. The average age of the cohort was 55.9 ± 12.5 years. Logistic regression analysis revealed that a greater number of non-Kuwaiti patients had anemia than Kuwaiti patients [adjusted odds ratio (aOR) = 1.34, 95% CI: 1.16-1.56; p < 0.001). Patients who received biologic treatment were more likely to be non-anemic [aOR = 1.33, 95% CI: 1.23-1.45; p < 0.001). Additionally, the study demonstrated that patients with anemia had greater odds of acquiring Disease Activity Score -28 joint count (DAS-28) ≥ 3.2 versus DAS-28 < 3.2 [aOR = 0.74, 95% CI: 0.61-0.90; p = 0.002].

CONCLUSIONS: Lower Hb levels in RA are an independent predictor of disease activity.

PMID:40196802 | PMC:PMC11973476 | DOI:10.5001/omj.2024.101

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Assessment of Quality of Life and Behavioral Problems in Children with Central Precocious Puberty

Oman Med J. 2024 Sep 30;39(5):e670. doi: 10.5001/omj.2024.100. eCollection 2024 Sep.

ABSTRACT

OBJECTIVES: We sought to estimate the impact of central precocious puberty (CPP) on psychosocial aspects in the cohort of children and to assess whether these aspects changed after treatment with gonadotropin-releasing hormone (GnRH) analogues.

METHODS: A case-control study enrolled 30 CPP children and 30 normal controls. The CPP group was assessed with emphasis on anthropometric measurements (Tanner staging for pubertal changes). The hormonal profile included gonadotropins, estradiol or testosterone, and GnRH stimulation test. The instruments used for neuropsychological assessment included the Arabic version of the pediatric quality of life inventory TM 4.0, the Child Behavior Checklist (CBCL), and IQ testing.

RESULTS: The mean study group age was 5.1 ± 2.3 years compared to 5.2 ± 2.2 years in the control group; 29 patients and 29 controls (96.7%) were females. CPP children had significantly lower scores than controls in health-related quality of life (QoL) domains except school functioning without significant changes in CBCL scores and cognitive function. There was a statistically significant improvement in these scores after they were treated with GnRH analogues for a year.

CONCLUSIONS: There are significant aberrations in CPP children’s QoL with no effect on behavior or cognition. After treatment with GnRH analogues for a year, QoL and CBCL T-scores showed a significant improvement.

PMID:40196800 | PMC:PMC11973446 | DOI:10.5001/omj.2024.100

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Identification of sentence stems characteristic of Chinese learner English writing

Heliyon. 2024 Aug 30;11(3):e37166. doi: 10.1016/j.heliyon.2024.e37166. eCollection 2025 Feb 15.

ABSTRACT

Phraseological units in academic English texts have been a central focus in recent corpus linguistic research. This paper describes a special category of clause-level phraseological units, namely, Characteristic Sentence Stems (CSSs), with a view to describing their identifying criteria and their extraction method. CSSs are contiguous lexico-grammatical sequences which contain a subject-predicate structure and which are frame expressions characteristic of academic writing. The extraction method of a CSS consists of six steps: POS tagging, n-gram segmentation, structure identification, significance of occurrence calculation, text range calculation, and overlapping sequence reduction. The significance of occurrence calculation is the crux of this method. It includes the computing of both the internal association and the boundary independence of a CSS, and it tests the occurring significance of the CSS from both the inside and the outside perspectives. Our methods and results suggest that CSSs can be statistically defined and extracted from corpora and can employed in large-scale studies to more fully account for the phraseological features of non-native English academic writing.

PMID:40196792 | PMC:PMC11947701 | DOI:10.1016/j.heliyon.2024.e37166

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The Effect of Proximal Cortical Screw Length of Volar Locking Plates on Clinical Outcomes in Distal Radius Fractures

Cureus. 2025 Apr 7;17(4):e81823. doi: 10.7759/cureus.81823. eCollection 2025 Apr.

ABSTRACT

Objective The aim of this study is to examine whether the length of the proximal diaphyseal screws of volar locking plates used in distal radius fractures affects the clinical outcomes. Material and methods The study included patients who were over 18 years of age and underwent volar locking plate application due to distal radius fracture with a minimum follow-up period of 12 months. Demographic data, Quick Disabilities of the Arm, Shoulder, and Hand (QDASH), grip strength, range of motion, and extensor tendon irritations were evaluated in patients. The prominence of the proximal cortical screws of the plates from the dorsal cortex was measured (in mm) on the lateral radiographs of the patients. Results The median follow-up time of the 73 patients in our study was 17 (14-26) months. The median age of the patients was 51 (44-58) years. Extensor tenosynovitis was detected in 22 patients due to proximal screw length. Proximal screw prominence over 1.2 mm was found to be statistically significant for extensor synovitis (p<0.05). Range of motion, radiological measurements, grip strength, QDASH, and other demographic data had no association with extensor tenosynovitis. Conclusion In the surgical treatment of distal radius fractures, dorsal cortex protrusion of proximal cortical screws of volar locking plates more than 1.2 mm plays a role in postoperative patient dissatisfaction.

PMID:40196763 | PMC:PMC11974232 | DOI:10.7759/cureus.81823

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Knowledge, attitudes, and practices regarding contraception amongst community pharmacy staff: a cross-sectional study in Nigeria

Front Reprod Health. 2025 Mar 24;7:1488707. doi: 10.3389/frph.2025.1488707. eCollection 2025.

ABSTRACT

INTRODUCTION: Lack of access to effective contraception methods can lead to an increased prevalence of unintended pregnancies, as well as possible deleterious health consequences. Community pharmacies represent the most accessible gateway for population medicines’ and healthcare needs. Regarding contraceptives, they have also been identified as a platform for the provision of additional services, such as complementary counselling. This study aimed at assessing the knowledge, attitudes, and practices of community pharmacy staff towards contraception.

METHODS: A cross-sectional study was undertaken in the Federal Capital Territory, Nigeria. Data were collected from 315 community pharmacy staff using self-administered questionnaires. The participants’ knowledge and attitude scores were categorised using Bloom’s cut-off point. Analyses were undertaken using Statistical Package for Social Sciences. The data were analysed using frequency distribution, chi-square, and linear regression at a 5% level of significance.

RESULTS: Male participants in the study (165/315, 52.4%) were slightly higher than the female respondents (150/315, 47.6%), and about two-thirds of the study cohort were pharmacists (200/315, 63.5%). The majority of the participants (183/315, 58.1%) had poor knowledge of contraceptive use. A quarter of them (81/315, 25.7%) reported moderate attitudes. Almost all the participants (279/298, 93.6%) indicated recommending contraceptives for married adults, and a significant proportion of them (136/292, 45.5%) were opposed to recommending contraceptives for unmarried adolescents. Study respondents’ professional role was also identified as a significant influence on their knowledge of contraceptives and contraception (p < 0.001).

CONCLUSION: Findings from this study revealed poor knowledge and negative attitudes of community pharmacy staff towards contraception. Government and relevant stakeholders can build on these novel findings to reform pertinent contextual policies and practices. This can significantly improve access to contraceptives amongst the populace, and consequently reduce unintended pregnancies alongside possible health and societal implications.

PMID:40196741 | PMC:PMC11973348 | DOI:10.3389/frph.2025.1488707