Search Results (216,711)

Background/Objectives: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Methods: The interactions of pinocembrin on drug transporters were determined in the Madin–Darby canine kidney (MDCK) cells overexpressing human (h)OAT1 or hOAT3 and in the Chinese hamster ovary (CHO-K1) cells overexpressing hOCT1, hOCT2, hMATE1, or hMATE2. The interactions of pinocembrin with BCRP and P-glycoprotein were determined in Caco-2 cells. The CYP450 enzyme inhibitory activity was assessed by a cell-free CYP450 screening assay. Results: Pinocembrin effectively inhibited the function of OAT1 and OAT3 with a half-inhibitory concentration (IC₅₀) and inhibitory constant (Ki) of ∼2 μM. In addition, it attenuated the toxicity of tenofovir, a substrate of hOAT1, in cells overexpressing hOAT1. Based on the kinetic study and molecular docking, pinocembrin inhibited OAT1 and OAT3 via a competitive inhibition. In contrast to hOAT1 and hOAT3, pinocembrin did not significantly inhibit the function of OCT1, OCT2, MATE1, MATE2, BCRP, and P-glycoprotein. In addition, pinocembrin potently inhibited the activity of CYP2C19, whereas it exhibited low inhibitory potency on CYP2B6 and CYP2C9. Conclusions: The present study reveals the potential drug interaction of pinocembrin on OAT1, OAT3, and CYP2C19. Co-administration with pinocembrin might affect OAT1-, OAT3-, and CYP2C19-mediated drug pharmacokinetic profiles. Full article

Background: This study compares system-reported organ doses (ODs) to manually calculated mean glandular doses (MGDs) in mammography across multiple centers and manufacturers in Dubai. Methods: A retrospective study of 2754 anonymized mammograms from six clinics in Dubai were randomly retrieved from a central dose survey database. Organ doses were documented along with other dosimetry information like kVp, mAs, filter, target, compression force, and breast thickness. Mean glandular doses, MGDs, were calculated manually for all the patients using the Dance formula and inferential statistical analyses were run to compare the two figures and verify the factors affecting each. Results: Our study’s analysis revealed that manually calculated mean glandular doses (MGDs) provide a more reliable indicator of radiation exposure than organ doses (ODs) reported by DICOM, particularly in multi-vendor scenarios. Manually calculated MGD values were consistently lower than system-reported ODs (MLO view: 0.96 ± 0.37 mGy vs. 1.38 ± 0.45 mGy; CC view: 0.81 ± 0.33 mGy vs. 1.22 ± 0.38 mGy). Significant differences in both system-reported ODs and manually calculated MGDs were observed across centers (p < 0.001). Strong correlations between system-reported ODs and manually calculated MGDs were found for Siemens equipment (r = 0.923, p < 0.001) but only moderate correlations for GE systems (r = 0.638, p < 0.001). Calculated MGD values were significantly higher for GE equipment compared to Siemens (1.49 ± 0.77 mGy vs. 0.93 ± 0.33 mGy, p < 0.001). Conclusions: This study addresses concerns regarding mammography dosimetry accuracy by demonstrating the superiority of mean glandular doses over DICOM-generated organ doses. These findings empower practitioners to optimize dose levels, ensuring safer and more effective breast cancer screening protocols. Full article

Background and Objective: This study aimed to examine the prevalence of dental fear among schoolchildren in Bosnia and Herzegovina, analyze the distribution of dental anxiety by gender, age, and place of residence in relation to perceived sources of fear, and evaluate its association with oral health status. Materials and Methods: The sample included 355 schoolchildren between the ages of 12 and 15. Data were gathered using a self-assessment questionnaire, a brief clinical oral examination, and the Children’s Fear Survey Schedule–Dental Subscale (CFSS-DS). Results: Clinical examinations showed that 87.61% of the children had dental caries, with a mean DMFT score of 3.75 (SD = 2.93). The prevalence of dental caries was significantly higher in the older group compared to the younger group (p < 0.01). Dental fear was present in 21.7% of the children, with a mean total CFSS-DS score of 27.50 (SD = 13.85). The most feared aspect among the children was “Choking” (73.8%), followed by “Injections” (63.7%) and “The noise of the dentist drilling” (52.1%). Children with dental fear had a significantly greater number of decayed and missing teeth, higher DMFT scores, and poorer gingival health and oral hygiene compared to those without dental fear (p < 0.01), even after adjusting for sociodemographic factors. Conclusions: The study found a moderate level of dental fear among Bosnian schoolchildren, with younger children and those from urban areas showing more fear of injections. It also showed a consistent link between dental anxiety and clinical factors such as caries, gum disease, and oral hygiene, even after adjusting for sociodemographic factors. Full article

Background: Despite evidence that low vision rehabilitation (LVR) services can improve visual function in patients with neovascular age-related macular degeneration (nAMD), many patients are not directed to access these resources. This study was conducted to determine factors associated with LVR referral and to assess the visual outcomes from completed evaluations. Methods: The study comprised a retrospective, cross-sectional analysis of patients with nAMD. Referrals for LVR services were extracted from the electronic health record (EHR). The effectiveness of each evaluation was determined by assessing the change in best corrected visual acuity (BCVA) achieved after distance refraction. Costs, quality-adjusted life years (QALYs), and incremental costs per-QALY-gained were calculated based upon the better-seeing eye by using a willingness-to-pay threshold of $50,000/QALY. Results: Out of 560 eligible patients with nAMD, 110 were referred for LVR (19.6%). Referral was more common for individuals who qualified as having low vision, based upon the visual acuity of the better-seeing eye (adjusted odds ratio [aOR], 3.214; 95% confidence interval [CI], 1.920–5.380, p < 0.001), had bilateral nAMD (aOR, 1.592; 95% CI, 1.017–2.492, p = 0.042), or had commercial health insurance compared to those who had Medicare (aOR, 2.887; 95% CI, 1.041–8.009, p = 0.042). Most patients referred completed LVR appointments (86%). More than half of the patients achieved improved BCVA for their better-seeing eye (53%) yielding an average gain of 0.04 QALYs/patient at a cost of $3504/QALY. The estimated net monetary benefit was $1704 per evaluation completed. Conclusions: Most patients with nAMD achieved improvements in visual function after low vision evaluation, yielding improvements in vision-related quality of life at a reasonable cost. Full article

Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS. A Somascan proteomic analysis of 12 MMPs, three of their inhibitors (TIMP-1, 2, 3), two ADAMS (9, 12), five ADAMTS (1, 4, 5, 13, 15), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor-1 (IGF-1) was undertaken in a well-validated PCOS database of 143 women with PCOS and 97 controls. Women with PCOS had significantly higher levels of MMP-9 and lower levels of MMP-2, MMP-14, TIMP-2, IGFBP-1, and IGF-1 compared to the controls (p < 0.0001, p < 0.005, p < 0.04, p < 0.05, p < 0.0001, and p < 0.0001, respectively). No differences were observed for any other MMPs. The ADAMS or ADAMTS levels did not differ between groups. Body mass index (BMI) was correlated with MMP-9 (p < 0.01), MMP-1 (p < 0.05), MMP-2 (p < 0.05), MMP-10 (p < 0.005), MMP-12 (p < 0.005), ADAM-9 (p < 0.05), and IGFBP-1 (p < 0.0001), but only MMP-9 still differed after accounting for BMI. MMP-9/TIMP-1, MMP-9/TIMP-2, and MMP-9/TIMP-3 ratios were higher in the PCOS group (p < 0.01), whilst MMP-17/TIMP-1 and MMP-17/TIMP-2 were lower (p = 0.01). MMP-2/TIMP ratios showed no difference between groups. TIMP-2 was positively correlated with CRP (p < 0.01). MMP changes in PCOS are largely driven by BMI, though increased MMP-9 is BMI-independent, suggesting that any deleterious effects of MMP-9 would be potentially exacerbated by a concomitantly increased BMI. The significant increases in the MMP-9/TIMP ratios suggests MMP-9 overactivity in PCOS. Full article

Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2–3% of the world’s population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM. Full article

Background: Noroviruses, which cause epidemic acute gastroenteritis, and Plasmodium parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of Plasmodium sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P₂₄ NP). Methods: We generated a unique P₂₄-αTSR NP by inserting the αTSR domain into a surface loop of the P domain. The P-αTSR fusion proteins were produced in the Escherichia coli expression system and the fusion protein self-assembled into the P₂₄-αTSR NP. Results: The formation of the P₂₄-αTSR NP was demonstrated through gel filtration, electron microscopy, and dynamic light scattering. A 3D structural model of the P₂₄-αTSR NP was constructed, using the known cryo-EM structure of the previously developed P₂₄ NP and P₂₄-VP8* NP as templates. Each P₂₄-αTSR NP consists of a P₂₄ NP core, with 24 surface-exposed αTSR domains that have retained their general conformations and binding function to heparan sulfate proteoglycans. The P₂₄-αTSR NP is immunogenic, eliciting strong antibody responses in mice toward both the norovirus P domain and the αTSR domain of Plasmodium CSP. Notably, sera from mice immunized with the P₂₄-αTSR NP bound strongly to Plasmodium sporozoites and blocked norovirus VLP attachment to their glycan receptors. Conclusion: These data suggest that the P₂₄-αTSR NP may serve as a combination vaccine against both norovirus and Plasmodium parasites. Full article

The mortality rate of ovarian cancer (OC) remains the highest among female gynecological malignancies. Advanced age is the highest risk factor for OC development and progression, yet little is known about the role of the aged tumor microenvironment (TME). We conducted RNA sequencing and lipidomic analysis of young and aged gonadal adipose tissue from rat xenografts before and after OC formation. The rates of tumor formation (p = 0.047) and tumor volume (p = 0.002) were significantly higher in the aged rats than in their young counterparts. RNA sequencing data showed significant differences in gene expression profiles between the groups of young and aged rat adipose tissues (p < 0.05), including S100a8, S100a9, Il1rl1, Lcn2, C3, Hba-a1, Fcna, and Pnpla3. At the time of tumor generation, there were also changes in the lipid components within the gonadal adipose tissues of young and aged rats, with higher levels of free fatty acids (FFAs) and triglycerides (TGs) in aged rats. Furthermore, the aged TME showed changes in immune cell composition, especially inflammation-related cells, including neutrophils, myeloid dendritic cells, CD4+ T cells (non-regulatory), and mast cell activation (p < 0.05). The correlation between S100a8, S100a9, neutrophil, and omega-5, FFA 18:3 levels was also determined. Additionally, omega-5, which is downregulated in aged rats, inhibited OC cell proliferation in vitro (p < 0.001). Our study suggests that the aged TME promotes OC proliferation resulting from age-related changes in gene/pathway expression, lipid metabolism, and immune cell distribution. Targeting the aging adipose microenvironment, particularly lipid metabolism, is a promising therapeutic strategy for OC and warrants further investigation. Significance: The aging microenvironment contributes to OC development and progression because of changes in the immune response regulatory genes S100a8 and S100a9, secreted by adipocytes, preadipocytes, or neutrophils, and by altering omega-5 metabolism. Full article

This study explores the relationship between forgiveness and interpersonal problem-solving skills among university students using a correlational design. The sample includes 443 students aged 18–26 from Mersin and Selçuk Universities, selected through convenience sampling. Data were collected using the Heartland Forgiveness Scale, the Interpersonal Problem-Solving Inventory, and a personal information form. Pearson correlation and multiple regression analyses were conducted. Results indicate significant relationships between forgiveness and problem-solving skills. Forgiveness positively predicts constructive problem-solving (r = 0.45, p < 0.01) and negatively correlates with negative approaches to problems (r = −0.37, p < 0.01), lack of self-confidence (r = −0.29, p < 0.01), and unwillingness to take responsibility (r = −0.31, p < 0.01). Forgiveness explains 25.2% of the variance in negative approaches, 8% in constructive problem-solving, 13.4% in self-confidence, and 10.3% in responsibility avoidance. Self-forgiveness, forgiveness of others, and situational forgiveness are significant predictors across these dimensions. Findings suggest that forgiving students manage interpersonal conflicts more positively, with reduced negative emotions and avoidance behaviors. Promoting forgiveness and problem-solving skills through educational programs may enhance students’ social harmony, adjustment, and life satisfaction, benefiting both individuals and society. This aligns with existing literature highlighting the emotional and relational benefits of forgiveness. Full article

Pathologies in neck and masticatory muscles affect muscle tone and biomechanical and viscoelastic properties, necessitating precise assessment for treatment. This study evaluated the impact of two guided interventions—relaxing exercises targeting the neck and masticatory muscles (“Exercise”) and heavy chewing using six chewing gums (“Chewing”)—on the masseter and upper trapezius muscles. Twelve participants (aged 19–40 years) underwent myotonometric assessment pre- and post-intervention, measuring tone, stiffness, decrement, relaxation time, and creep. The results showed significant changes in the masseter muscle after exercise, with increased stiffness (14.46%, p < 0.001) and tone (7.03%, p < 0.001) but decreased creep (−9.71%, p < 0.001) and relaxation time (−11.36%, p < 0.001). Conversely, chewing decreased stiffness (−8.82%, p < 0.001) and tone (−5.53%, p < 0.001), while it increased creep (9.68%, p < 0.001) and relaxation time (9.98%, p < 0.001). In the trapezius muscles, tone decreased after both interventions (Exercise: −7.65%, p < 0.001; Chewing: −1.06%, p = 0.003), while relaxation increased (Exercise: 1.78%, p < 0.001; Chewing: 2.82%, p < 0.001). These findings reveal the distinct effects of exercise and chewing on muscle properties, emphasising the complexity of their therapeutic potential and the need for further investigation. Full article

Background/Objectives: To examine the combined effects of sleep quality, dual tasks, and load carriage on postural stability. Methods: Twenty-three university student participants (12 males, ages: 24.6 ± 6.1 year) completed the Pittsburgh Sleep Quality Index (PSQI), then performed quiet standing and a dual task while standing on force plates with and without load carriage. Correlations and repeated measures analysis of variances were used to assess relationships, main effects, and interaction effects of tasks on center of pressure (COP) to assess postural stability. Both a traditional PSQI global score and a sensitivity analysis of the PSQI cut-off were conducted. Results: With the traditional PSQI criteria, a main effect of sleep quality on 95% ellipse area was observed, with good sleepers outperforming bad sleepers (p = 0.016). Additionally, a significant interaction between sleep quality and task (p = 0.049) indicated that COP anterior–posterior velocity was lower during the dual task for good sleepers. No effects on sleep quality or interaction were found for other COP measures. The sensitivity analysis yielded no effect on sleep quality or interaction effects on any COP measure. There were no significant correlations between the PSQI global scores and COP variables. Conclusions: Overall, the results indicate that sleep quality alone had a limited effect and did not significantly interact with dual tasks or load carriage during quiet standing. Practitioners working with individuals who commonly experience poor sleep quality and perform load carriage and dual tasks should consider that common COP screens to assess postural stability may not detect differences due to self-reported sleep quality in healthy, young adults. Full article

Background/Objectives: Most studies on the interaction between the immune system and cancer focus on T-cells, whereas studies on tumor-infiltrating B-lymphocytes (TIL-Bs) are still underrepresented. The aim of this study was to assess the prognostic impact of TIL-Bs in early- and advanced-stage oral cavity squamous cell carcinoma (OCSCC). Methods: In total, 222 OCSCCs were studied. Consecutive sections were stained for CD45 and CD19. OCSCCs were categorized as either “TIL-B-rich” or “TIL-B-poor”, and the survival of both groups was analyzed. Similar analyses were performed for CD45+ TILs and the CD19/CD45 ratio. Matched subgroups of twelve TIL-B-rich and TIL-B-poor tumors were stained for CD3 and CD8 to determine differences in T-cell infiltration, and further spatial interaction between T- and B-cells was evaluated in six samples. Results: Five-year OS was 75.0% for TIL-B-rich and 54.2% for TIL-B-poor OCSCCs (p < 0.001). The survival benefit of TIL-B-rich OCSCCs remained significant after correction for the histopathological characteristics (p = 0.033). While for early-stage tumors, TIL-B richness benefited OS independent of demographic-, clinical, or histopathological features, for advanced-stage disease, this was not the case, although a clear benefit of a TIL-B-rich status was observed, specifically up until 36 months after diagnosis. TIL-B-rich tumors contained more CD3+ TILs (p = 0.007), but not CD8+ TILs. Spatial characterization suggested that TIL-Bs mostly co-localized with CD3+CD8− TILs and that this interaction was increased in TIL-B-rich OCSCC. Conclusions: The presence of TIL-Bs is associated with a more favorable prognosis in OCSCC, in particular for early-stage disease. Full article

Numerous studies have demonstrated that Broussonetia papyrifera is an unconventional feed resource with significant developmental potential. This research aimed to explore the effects of Broussonetia papyrifera silage on the growth performance, blood parameters, immunity, antioxidation, cytokine levels, and rumen bacterial composition of Kazakh lamb. Forty healthy male Kazakh lambs, aged 5 months and weighing 30.12 ± 1.14 kg, were randomly divided into control and experimental groups, each consisting of four replicates (five lambs per replicate). The control group was fed a basal diet, while the experimental group received a diet supplemented with 20% Broussonetia papyrifera silage (dry matter basis). Following a 10-day pre-feeding period, a 60-day formal experiment was conducted. The results indicated no significant difference in growth performance between the experimental and control groups. However, compared to the control group, the use of Broussonetia papyrifera silage significantly reduced (p < 0.05) neutrophil, lymphocyte, and eosinophil counts, as well as creatinine levels in the blood. Furthermore, Broussonetia papyrifera silage (p < 0.01) enhanced total serum antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, immunoglobulin A, immunoglobulin M, immunoglobulin G, interleukin-2, interleukin-6, and interleukin-8, and decreased malondialdehyde and interleukin-4 levels. Additionally, the use of Broussonetia papyrifera silage increased the diversity and richness of the rumen bacterial community, notably enhancing the relative abundance of Firmicutes such as Rikenellaceae_RC9_gut_group and Christensenellaceae_R-7_group. In conclusion, feeding Kazakh lamb with Broussonetia papyrifera silage (20% DM) did not adversely affect their growth performance but improved their immunity and antioxidant capacity and enhanced the relative abundance of beneficial bacteria in the rumen, thereby promoting animal health. Full article

The solid waste generated from processing rosehip fruits into jam is valuable due to its rich content in fibres, polyphenols, and carotenoids; it could be valorised as a functional ingredient in a powder form to enrich food products. This study aimed to test its potential as a value-added ingredient, especially to enrich waffle cones with fibres, polyphenols, and carotenoids. In this regard, four formulations of waffle cones were prepared by partially substituting wheat flour with rosehip waste powder at 0%, 10%, 15%, and 20%, reaching concentrations of 0%, 3.7%, 5.7%, and 7.5% of the total batter, respectively. These were assessed for their sensory, textural, and techno-functional properties; proximate composition (including crude fibre); energy value; pH; and colour, as well as the content of carotenoids and polyphenols. The contribution of rosehip powder to the production cost of these waffle cone formulations was also determined. The results showed that using rosehip waste powder as an ingredient reduced the waffle cones powder’s capacity to hold water (from 3.11 g/g to 2.64–3.08 g/g) and to swell (from 4.98 mL/g to 4.23–4.48 mL/g), while it increased their oil-holding capacity (from 0.93 g/g to 0.96–1.19 g/g) and the content in fibre (from 1.58% to 3.41–4.83%), polyphenols (from 400.70 µg/g to 1732.26–2715.69 µg/g), and carotenoids (from n.d. to 6.86–14.28 µg/g); however, the solubility (72.65–75.33%), hardness (2.31–2.83 N), and fracturability (6–8) were not significantly influenced. The sensory acceptability of enriched waffle cones (92–93%) was higher than that of control waffle cones (90%). The production cost of a waffle cone increased by EUR 0.004–0.009 when wheat flour was substituted by rosehip powder in concentrations of 10–20%. In conclusion, to enrich waffle cones with fibres, polyphenols, and carotenoids, at least 10% of wheat flour must be substituted with rosehip waste powder in their manufacturing recipe. Full article

While ultraviolet C (UVC) radiation has beneficial applications, it can also pose risks to living organisms. Nevertheless, a detailed assessment of UVC radiation’s effects on mammalian male reproductive physiology, including the underlying mechanisms and potential protective strategies, has not yet been accomplished. This study aimed to examine the critical roles of oxidative stress, autophagy, reproductive hormonal axis, and microRNAs in UVC-induced reproductive challenges in male rats. Semen, biochemical, molecular, and in silico analyses revealed significant dysregulation of testicular steroidogenesis, impaired spermatogenesis, deteriorated sperm quality, and altered reproductive hormonal profiles, which ultimately lead to a decline in fertility in male rats exposed to UVC radiation. Our data indicated that the suppression of autophagy, stimulation of gonadotropin-inhibiting hormone (GnIH), and alteration of microRNAs serve as key mediators of UVC-induced stress effects in mammalian reproduction, potentially contributing to male infertility. Targeting these pathways, particularly through pretreatment with hesperidin (HES), offers a promising strategy to counteract UVC-induced male infertility. In conclusion, the present findings emphasize the importance of understanding the molecular mechanisms behind UVC-induced male infertility and offer valuable insights into the protective mechanisms and prospective role of HES in safeguarding male reproductive health. Full article