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Kidney transplantation (KT) is the optimal form of renal replacement therapy for patients with end-stage renal diseases. However, this health service is not available to all patients, especially in developing countries. The deceased donor KT programs are mostly absent, and the living donor KT centers are scarce. Single-center studies presenting experiences from developing countries usually report a variety of challenges. This review addresses these challenges and the opposing strategies by reviewing the single-center experiences of developing countries. The financial challenges hamper the infrastructural and material availability, coverage of transplant costs, and qualification of medical personnel. The sociocultural challenges influence organ donation, equity of beneficence, and regular follow-up work. Low interests and motives for transplantation may result from high medicolegal responsibilities in KT practice, intense potential psychosocial burdens, complex qualification protocols, and low productivity or compensation for KT practice. Low medical literacy about KT advantages is prevalent among clinicians, patients, and the public. The inefficient organizational and regulatory oversight is translated into inefficient healthcare systems, absent national KT programs and registries, uncoordinated job descriptions and qualification protocols, uncoordinated on-site investigations with regulatory constraints, and the prevalence of commercial KT practices. These challenges resulted in noticeable differences between KT services in developed and developing countries. The coping strategies can be summarized in two main mechanisms: The first mechanism is maximizing the available resources by increasing the rates of living kidney donation, promoting the expertise of medical personnel, reducing material consumption, and supporting the establishment and maintenance of KT programs. The latter warrants the expansion of the public sector and the elimination of non-ethical KT practices. The second mechanism is recruiting external resources, including financial, experience, and training agreements.
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Cumin seeds are frequently utilized in herbal infusions and as flavoring agents in home cuisine. Nevertheless, studies have demonstrated that spices are frequently contaminated with pathogenic bacteria, including bacterial spores. The aim of this study was to assess the effectiveness of a new decontamination method called "Intensification of Vaporization by Decompression to the Vacuum" (IVDV) on intentionally contaminated Cuminum cyminum seeds. The study also examined the impact of this treatment on the color and oil profile of the treated samples. The untreated samples were inoculated with Escherichia coli (ATCC 25922) and Salmonella Typhimurium (ATCC 14028) and then subjected to IVDV treatment. Response surface methodology was employed to obtain safe, high-quality cumin seeds presenting a balance between microbial load, color, and oil profile. The optimal IVDV conditions were achieved at a pressure of 3.5 bar and a time of 133.45 s, resulting in typical 4 log reductions observed with 99.99% of Escherichia coli and Salmonella Typhimurium inactivation. The treated spices presented a mild color modification compared to the untreated ones, manifested by a darker shade (decreased L* value), reduced greenness (increased a* value), and heightened yellowness (increased b* value). The GC-MS analysis detected the existence of seven compounds in the treated cumin, with cuminaldehyde being the primary compound (83.79%). Furthermore, the use of IVDV treatment resulted in an increase in the total content of essential oils in some samples, whereby six monoterpenes were identified in the untreated sample compared to seven monoterpenes in IVDV-treated samples. This innovative technology demonstrated high efficacy in decontaminating C. cyminum seeds, improving the extractability of the essential oils while only slightly affecting the color.
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Diabetic cardiomyopathy (DCM) is a major complication of type 2 diabetes mellitus (T2DM) that leads to significant morbidity and mortality. The alteration in the signaling mechanism in diabetes leading to cardiomyopathy remains unclear. The purpose of this study is to investigate the role of tauopathy in myocardial dysfunction observed in T2DM. In that regard, diabetic Sprague Dawley rats were treated with intraperitoneal injections of lithium chloride (LiCl), inhibiting tau phosphorylation. Cardiac function was evaluated, and molecular markers of myocardial fibrosis and the TGF-ß signaling were analyzed. T2DM rats exhibited a decline in ejection fraction and fractional shortening that revealed cardiac function abnormalities and increased myocardial fibrosis. These changes were associated with tau hyperphosphorylation. Treating diabetic rats with LiCl attenuated cardiac fibrosis and improved myocardial function. Inhibition of GSK-3ß leads to the suppression of tau phosphorylation, which is associated with a decrease in TGF-ß expression and regulation of the pro-inflammatory markers, suggesting that tau hyperphosphorylation is parallelly associated with fibrosis and inflammation in the diabetic heart. Our findings provide evidence of a possible role of tau hyperphosphorylation in the pathogenesis of DCM through the activation of TGF-ß and by inducing inflammation. Targeting the inhibition of tau phosphorylation may offer novel therapeutic approaches to reduce DCM burden in T2DM patients.
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The study highlighted the potential of sesame seed coat (SSC), typically discarded during sesame paste processing, as a valuable resource for valorization through extracting bioactive compounds. It examined the phenolic composition and antioxidant activity of SSC, and evaluated its antibacterial properties against foodborne pathogens such as Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella Typhimurium. Additionally, SSC underwent nanoemulsion coating, analyzed using dynamic light scattering and scanning electron microscopy, to enhance its application as a natural preservative. The research specifically focused on incorporating SSC nanoemulsion into milk to determine its effectiveness as a preservative. SSC demonstrated considerable antioxidant activity and phenolic content, with catechin identified as the predominant polyphenol. GC-MS analysis revealed seven major compounds, led by oleic acid. Notably, SSC effectively inhibited L. monocytogenes in broth at 100 mg/ml. The application of SSC and its nanoemulsion resulted in changes to bacterial morphology and a significant reduction in bacterial counts in milk, highlighting its potential as an effective natural antibacterial agent. The findings of this study highlight the potential use of SSC as a valuable by-product in the food industry, with significant implications for food preservation.
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INTRODUCTION: Objective Structured Clinical Examinations (OSCEs) are essential assessments for evaluating the clinical competencies of medical students. The COVID-19 pandemic caused a significant disruption in medical education, prompting institutions to adopt virtual formats for academic activities. This study analyzes the feasibility, satisfaction, and experiences of pediatric board candidates and faculty during virtual or electronic OSCE (e-OSCE) training sessions using Zoom video communication (Zoom Video Communications, Inc., San Jose, USA). METHODS: This is a post-event survey assessing the perceptions of faculty and candidates and the perceived advantages and obstacles of e-OSCE. RESULTS: A total of 142 participants were invited to complete a post-event survey, and 105 (73.9%) completed the survey. There was equal gender representation. More than half of the participants were examiners. The overall satisfaction with the virtual e-OSCE was high, with a mean score of 4.7±0.67 out of 5. Most participants were likely to recommend e-OSCE to a friend or colleague (mean score 8.84±1.51/10). More faculty (66.1%) than candidates (40.8%) preferred e-OSCE (P=0.006). CONCLUSION: Transitioning to virtual OSCE training during the pandemic proved feasible, with high satisfaction rates. Further research on virtual training for OSCE in medical education is recommended to optimize its implementation and outcomes.
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When feasible from an oncologic standpoint, partial penectomy (PP) is often preferred to total penectomy (TP) for penile cancer treatment, for the preservation of functional urinary outcomes. However, to date, there has not been a direct comparison of perioperative outcomes between PP and TP. Comparing treatments for penile cancer has proven difficult due to the rarity of penile cancer in the United States. We aimed to report differences in pre-operative risk factors, intra-operative outcomes, and postoperative outcomes between TP and PP for penile cancer. Using the National Surgical Quality Improvement Program database, we conducted a retrospective cohort review of penile cancer patients enlisted in the database between the years 2006-2016 using the International Classification of Diseases clinical modification 9th revision codes. A total of 260 patients, 67 TP and 193 PP patients, were included. PP patients were less likely to be transferred patients (p = 0.002), diabetic (p = 0.026), and were more likely to have preoperative laboratory values within normal limits. PP patients also had shorter lengths of stay in the hospital (p < 0.001) and operating time (p < 0.001). Significant differences were also found for inpatient stay (p < 0.001), 30-day post-surgery complications (p < 0.001), deep incisional surgical site infection (SSI) (p = 0.017), wound disruption (p = 0.017), intraoperative or postoperative transfusion (p = 0.029), and sepsis (p < 0.005). Finally, PP patients required fewer concurrent surgical procedures (p < 0.001). Demographic differences between PP and TP patients may reflect patients presenting with more advanced oncologic disease. PP is associated with fewer postoperative complications, shorter surgeries, shorter hospital stays, fewer concurrent surgical procedures, and comorbid conditions compared to TP. A gap remains in the reported data pertaining to postoperative sexual function and erectile outcomes for PP at a national level.
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This study focused on testing the antibacterial and antifungal activity of Origanum syriacum (O. syriacum) and Cimbopogon winterianus (C. winterianus) extracts and their essential oils (EOs). The bacteria were isolated from urine samples and identified by a VITEK assay, and the fungi were isolated from spoiled food samples and further identified by MALDI-TOF. The susceptibility of the microbial isolates was assessed by determining the bacteriostatic and bactericidal/fungicidal effects by the minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) broth microdilution assay and time-kill test. The antibiofilm activities were assessed by the antibiofilm screening assays. The bacterial isolates included three Gram-negative isolates (Escherichia coli, Klebsiella pneumonia, and Citrobacter freundii) and two Gram-positive isolates (Staphylococcus aureus and Streptococcus intermedius). The fungal isolates included Candida albicans and Aspergillus niger. The O. syriacum and C. winterianus extracts exhibited bacteriostatic and fungistatic activities (MIC 1.25-2.5 mg/mL for the bacterial isolates and 2.5-5 mg/mL for the fungal isolates). However, their EOs exhibited bactericidal (MBC 5-20%) and fungicidal (MFC 1.25-10%) activities, meaning that the EOs had a better antimicrobial potential than the extracts. The antibiofilm activities of the mentioned extracts and their EOs were relatively weak. The O. syriacum extract inhibited S. aureus, S. intermedius, and K. pneumonia biofilms at a concentration of 0.3125 mg/mL and C. albicans and A. niger biofilms at 0.625 mg/mL. No antibiofilm activity was recorded for C. winterianus extract. In addition, the packaging of grapes with C. winterianus extract preserved them for about 40 days. The results reflect the significant antimicrobial activity of O. syriacum and C. winterianus extracts and their EOs, thus suggesting their potential in food packaging and preservation.
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Objective: The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high-grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery. Methods: All patients diagnosed with high-grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan-Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival. Results: A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow-up period was 29.2 months. Notably, group 2 demonstrated significantly enhanced overall and metastasis-free survival rates compared to group 1. At 47.8 months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis-free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6 months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002. Conclusion: Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high-grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.
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In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast. We have found that we can revert zebrafish support cells back to a migratory progenitor state by pharmacologically altering the signaling environment to mimic that of the migratory primordium, with active Wnt signaling and repressed FGF signaling. The reverted supporting cells migrate anteriorly and posteriorly along the horizontal myoseptum and will re-epithelialize to form an increased number of neuromasts along the midline when the pharmacological agents are removed. These data demonstrate that supporting cells can be readily reprogrammed to a migratory multipotent progenitor state that can form new sensory neuromasts, which has important implications for our understanding of how the lateral line system matures and expands in fish and also suggest avenues for returning mammalian supporting cells back to a proliferative state.
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Movimento Celular , Sistema da Linha Lateral , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Sistema da Linha Lateral/embriologia , Sistema da Linha Lateral/citologia , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Via de Sinalização Wnt , Fatores de Crescimento de Fibroblastos/metabolismo , Diferenciação Celular , Células-Tronco/metabolismo , Células-Tronco/citologia , Transdução de Sinais , Reprogramação CelularRESUMO
BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Proteínas Supressoras de Tumor , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Proteínas Supressoras de Tumor/genética , Hepatite C/complicações , Hepatite C/virologia , Hepatite C/diagnóstico , Hepatite C/genética , Hepacivirus/genética , Idoso , Regulação Neoplásica da Expressão Gênica , Adulto , Curva ROC , Relevância ClínicaRESUMO
Magnetic nanoparticles have emerged as a promising tool for wastewater treatment due to their unique properties. In this regard, Co0.33Mg0.33Ni0.33SmxFe2-xO4 (0.00 ≤ x ≤ 0.08) nanoparticles were prepared to examine their magnetic separation efficiency (MSE), photocatalytic, antibacterial, and antibiofilm performances. Pure nanoparticles, having the highest saturation magnetization (Ms = 31.87 emu/g), exhibit the highest MSE, where 95.6% of nanoparticles were separated after 20 min of applying a magnetic field of 150 mT. The catalytic performance of the prepared samples is examined by the photodegradation of rhodamine B (RhB) dye exposed to direct sunlight radiation. Improved photocatalytic activity is exhibited by Co0.33Mg0.33Ni0.33Sm0.04Fe1.96O4 nanoparticles, labeled as Sm0.04, where the rate of the degradation reaction is enhanced by 4.1 times compared to pure nanoparticles. Rising the pH and reaction temperature improves the rate of the photodegradation reaction of RhB. The incorporation of 15 wt% reduced graphene oxide (rGO) with Sm0.04 enhanced the rate of the reaction by 1.7 and 2.4 times compared with pure Sm0.04 sample and rGO, respectively. The antibacterial and antibiofilm activities against Escherichia coli, Leclercia adecarboxylata, Staphylococcus aureus, and Enterococcus faecium are assessed by the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) broth microdilution, the agar well diffusion, the time-kill assays, the biofilm formation, and destruction assays. The bacteria used in these assessments are isolated from wastewater. The nanoparticles exhibit a bacteriostatic activity, with a better effect against the Gram-positive isolates. Co0.33Mg0.33Ni0.33SmxFe2O4 (x = 0.00) nanoparticles have the best effect. The effect is exerted after 2-3 h of incubation. Gram-positive biofilms are more sensitive to nanoparticles.
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Antibacterianos , Luz Solar , Antibacterianos/farmacologia , Antibacterianos/química , Catálise , Fotólise , Rodaminas/química , Biofilmes/efeitos dos fármacosRESUMO
Obsessive-compulsive disorder (OCD) is a disabling disease characterized by distressing obsessions and repetitive compulsions. The etiology of OCD is poorly known, and mouse modeling allows to clarify the genetic and neurochemical basis of this disorder and to investigate potential treatments. This study evaluates the impact of the 5-HT1B agonist RU24969 on the induction of OCD-like behaviours in female BALB/c mice (n = 30), distributed across five groups receiving varying doses of RU24969. Behavioural assessments, including marble test, tail suspension test, sucrose preference test, forced swim test, and nestlet shredding test, were conducted. Gene expression and protein quantitation of Gabra1 and serotonin transporter in mouse brain were also performed. Marble-burying behaviour increased significantly at high doses of RU24969 (15-20 mg/kg). The forced swimming test consistently showed elevated values at the same high concentrations, compared to the control. Altered reward-seeking behaviour was indicated by the sucrose preference test, notably at 15 and 20 mg/kg doses of RU24969. Nestlet shredding results did not show statistical significance among the tested animal groups. Gene expression analysis revealed reduced Gabra1 expression with increasing doses of RU, while serotonin transporter was not related to varying doses of RU24969. Western blotting corroborated these trends. The results underscore complex interactions between the serotonin system, GABAergic signaling, and OCD-relevant behaviours and suggest the use of intraperitoneal injection of 15 mg/kg of RU24969 to induce OCD-like behaviour in BALB/c mouse models.
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Transtorno Obsessivo-Compulsivo , Feminino , Camundongos , Animais , Camundongos Endogâmicos BALB C , Transtorno Obsessivo-Compulsivo/genética , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Carbonato de Cálcio , SacaroseRESUMO
Anthropogenic activities over the past half-century have had a negative impact on the wetland ecosystem in the Nile Delta, which provides essential provisioning and regulating services. Therefore, it is crucial to systematically investigate pollution levels and their ecological consequences at both spatial and temporal scales in order to promote sustainable development. In this study, data on metal pollution in the Manzala Lake were compiled through a systematic review of all published literature from 1968 to 2020. Additionally, agricultural data (including land use, pesticide and fertilizer usage, and discharge) and economic data for the same time period were collected to identify the main drivers of pollution. The results indicated an overall increasing trend in heavy metal concentrations during the study period. The average concentrations of metals, arranged in descending order, were as follows: Fe (15,115.5 µg/g) > Mn (722 µg/g) > Zn (115.4 µg/g) > Cu (65.9 µg/g) > Ni (62.5 µg/g) > Cr (58.1 µg/g) > Pb (54.1 µg/g) > Cd (4.7 µg/g) > Hg (0.1 µg/g). A linear regression model revealed that wastewater discharge, water reuse, and the use of pesticides and fertilizers are the main sources of heavy metal pollution in the Manzala Lake. Consequently, there has been a dramatic decrease in the biodiversity of fish and molluscan communities. The study also found a correlation between heavy metal pollution and socio-economic development, highlighting the urgent need for attention to the conservation, management, and sustainable development of the lake.
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Metais Pesados , Praguicidas , Poluentes Químicos da Água , Ecossistema , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Medição de Risco , Metais Pesados/análise , Lagos , ChinaRESUMO
(1) Background: Cumin seeds, extracted from the plant Cuminum cyminum, are abundant in phenolic compounds and have been extensively researched for their chemical makeup and biological effects. The objective of this research is to enhance the water extraction of polyphenols through the water bath (WB) technique and to evaluate the antiradical, antibacterial, and anticancer effects of the extract. (2) Methods: Response Surface Methodology was used to find the best parameters to extract polyphenols. Three experimental parameters, time, temperature, and solid-liquid ratio, were tested. The disc diffusion method has been used to determine the antimicrobial activities against Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans. The antiradical activity was performed using the DPPH method, while total phenolic content was performed using Folin-Ciocalteu. High-Performance Liquid Chromatography (HPLC) was conducted to analyze the phytochemical profile of WB extracts. The anticancer activity of the lyophilized extract was assessed against three cancer cell lines (colon (HT29), lung (A549), and breast (MCF7) cancer cell lines).; (3) Results: The optimal conditions for water extraction were 130 min at 72 °C. The total phenolic compounds yield (14.7 mg GAE/g DM) and antioxidant activity (0.52 mg trolox eq./mL) were obtained using a 1:40 solid-liquid ratio. The primary polyphenols identified were the flavonoids rutin (0.1 ppm) and ellagic acid (3.78 ppm). The extract had no antibacterial or antifungal activities against the microorganisms tested. The extract showed anticancer activity of about 98% against MCF7 (breast cancer cell line), about 81% against HT29 (colon cancer cell line), and 85% against A549 (lung cancer cell line) at high doses. (4) Conclusions: Extraction time and a high solid-liquid ratio had a positive impact on polyphenol recovery and in maintaining their quantity and quality. Furthermore, the optimal aqueous extract exhibited strong antiradical activity reflected by the inhibition of free radicals in addition to a significant specificity against the tested cancer cell lines.
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OBJECTIVES: Improving response rates in colorectal cancer (CRC) is an urgent clinical need. This study aimed to explore the synergistic action of Lebanese rosemary essential oil (REO) and 5-fluorouracil (5-FU) in HCT116 CRC cells. METHODS: We tested the cell viability of monotherapy and combination therapy. The combination index was calculated using CompuSyn software to evaluate drug-drug interactions and the level of synergistic cytotoxicity. We also evaluated cell migration and cytopathology. Furthermore, cell apoptosis-related proteins (i.e. Bax and Bcl-2) were measured by Western blot analysis. KEY FINDINGS: The REO/5-FU combination synergistically reduced cell viability, effectively decreased cell migration, and increased the Bax/Bcl-2 ratio in HCT116 cells. This triggered a proapoptotic morphology and initiated an apoptotic cascade in HCT116 cells, as indicated by a higher Bax/Bcl-2 ratio. CONCLUSIONS: Our results provide evidence of the REO/5-FU combination as a better approach to improve 5-FU anticancer efficacy and allow the use of lower 5-FU doses due to the adjuvant effect of REO.
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Apoptose , Sobrevivência Celular , Neoplasias Colorretais , Sinergismo Farmacológico , Fluoruracila , Óleos Voláteis , Proteínas Proto-Oncogênicas c-bcl-2 , Proteína X Associada a bcl-2 , Humanos , Fluoruracila/farmacologia , Óleos Voláteis/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Células HCT116 , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Movimento Celular/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Rosmarinus/químicaRESUMO
BACKGROUND: Clinical trials have demonstrated the efficacy and safety of mitral transcatheter edge-to-edge repair (M-TEER) for selected patients with severe mitral regurgitation. However, the generalizability of trial results to real-world patients remains uncertain. OBJECTIVES: The authors aimed to compare baseline characteristics and in-hospital outcomes among trial participants with nonparticipants undergoing M-TEER. METHODS: Using the National Inpatient Sample database years 2016-2020, M-TEER admissions were identified and categorized into trial participants vs none. We also identified a cohort of trial noneligible patients based on clinical exclusion criteria from pivotal trials. Multivariate regression analysis was performed to compare in-hospital outcomes. The primary outcome was in-hospital mortality, and secondary outcomes included in-hospital complications, length of stay, and hospitalization cost. RESULTS: Among 38,770 M-TEER admissions from 2016 to 2020, 11,450 (29.5%) were trial participants, 22,975 (59.3%) were eligible nonparticipants, and 2,960 (7.6%) were noneligible. Baseline characteristics and comorbidity profiles were mostly similar between trial participants vs eligible nonparticipants. In-hospital mortality (adjusted OR [aOR]: 0.98; 95% CI: 0.60-1.62), cardiogenic shock (aOR: 1.06; 95% CI: 0.80-1.42), mechanical circulatory support (aOR: 0.91; 95% CI: 0.58-1.41), mechanical ventilation (aOR: 1.03; 95% CI: 0.74-1.42), and conversion to mitral valve surgery (aOR: 1.08; 95% CI: 0.57-2.03) were not different between both groups. Conversely, M-TEER for noneligible patients was associated with higher rates of mortality (aOR: 6.27; 95% CI: 3.75-10.45) and complications. CONCLUSIONS: The majority of real-world M-TEER patients would have been eligible for clinical trial participation and had comparable clinical profiles and in-hospital outcomes to trial participants. However, noneligible patients had worse in-hospital outcomes compared with trial participants.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Resultado do Tratamento , Hospitais , Pacientes Internados , Bases de Dados Factuais , Mortalidade Hospitalar , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversosRESUMO
The influence of broiler age on the apparent metabolizable energy (AME) and nitrogen-corrected AME (AMEn) of meat and bone meal (MBM) was investigated. A corn-soy basal diet and an experimental diet wherein 300 g/kg of the basal diet was replaced (w/w) with MBM were developed. The diets, in pellet form, were fed to six replicate cages across six age groups, namely d 1 to 7, 8 to 14, 15 to 21, 22 to 28, 29 to 35 or 36 to 42 d post-hatch. Birds were fed either a starter diet from d 1-21 or a finisher diet from d 22-35. Basal and experimental diets were introduced on d 1, 8, 15, 22, 29 and 36 with 10 (d 1-7), 8 (d 8-14) and 6 (d 15-42) birds per replicate. Total collection of excreta was carried out during the last 4 d of each age period. A linear decrease (p < 0.001) in the retention of dry matter and nitrogen was observed with advancing age. The AMEn of MBM showed a linear increase (p < 0.05), rising from 12.56 MJ/kg during d 1-7 to 13.90 MJ/kg during d 29-35, followed by a decline to 13.41 MJ/kg during d 36-42. The current findings showed that the energy utilization of MBM increased with the advancing age of broilers. Age-dependent AMEn values of MBM may need to be considered when MBM is included in feed formulations.
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Background: Thyroid hormones (THs) signaling has profound effects on many physiological processes. The regulation of THs signaling in various tissues involves the action of microRNAs (miRNAs) on thyroid deiodinases and receptors. THs regulate the expression of certain miRNAs and their target messenger RNAs (mRNAs) in various tissues and cells. The modulation of miRNA levels by THs affects their functions in processes such as liver lipid metabolism, skin physiology, and muscle and heart performance. Aim: This research aimed to investigate miR-181b, miR-206, and miR-21 in the serum of patients with subclinical and overt hypothyroidism to determine their possible role in the diagnosis of the disease and their relationship to clinical disorders related to hypothyroidism. Methods: This study included ninety participants, divided evenly into three groups as follows: patients with overt hypothyroidism diagnosed clinically, radiologically, and by investigation, subclinical hypothyroid patients, and healthy volunteers. The patients had a thorough medical history and underwent a clinical examination. Laboratory tests included plasma cholesterol, LDL, HDL, TGs, liver and renal function tests, CBC, fasting insulin, HOMA-IR, HbA1c, TSH, and free T4. The serum levels of miR-21, miR-206, and miR-181b were measured using qRT-PCR. Results: miR-206 and miR-181b levels were higher in the subclinical group, followed by the hypothyroid and control groups. For miR-21, there was a significantly lower mean value in both the hypothyroid and subclinical groups than in the control group, with no difference between the two groups. Both miR-206 and miR-181b showed a significant negative association with albumin and free T4 levels and a significant direct association with GGT, ALT, AST, creatinine, uric acid, TGs, TC, LDL, TSH, thyroid volume, and CAP score. The same correlation pattern was observed for miR-181b, except that it was not significantly correlated with the TGs. For miR-21 levels, there was a significant positive correlation with albumin, free T4 level, and kPa score and a negative correlation with GGT, ALT, AST, creatinine, uric acid, HOMA-IR, HbA1c, TC, LDL, TSH, and CAP score. Cases with F1 kPa score and S2 CAP scores had significantly higher averages for miR-206 and miR-181b, with a p-value of 0.05. Moreover, miR-21 levels were significantly lower in the S2 CAP score group. Conclusion: These miRNAs (miR-206, miR-181b, and miR-21) may be used as diagnostic biomarkers for hypothyroidism. They may be used as therapeutic targets to control dyslipidemia and hepatic steatosis during hypothyroid disease.
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BACKGROUND & AIMS: Inflammatory bowel disease (IBD), involving both Crohn's disease (CD) and ulcerative colitis (UC), represents a chronic, immune-mediated inflammatory disease due to an uncontrolled, ongoing inflammatory response to intestinal bacteria in those with genetic susceptibility. MicroRNA (miRNA) extrusion from relevant remote organs or tissues is reflected in the expression of miRNAs in serum and plasma. Both UC and CD patients had higher blood levels of expressed miR-199a. Long noncoding RNA (lncRNA) ANRIL is a proinflammatory gene that mediates nuclear factor κB to play a role in inflammatory diseases, such as IBD. The aim of the current study is to investigate the potential role of both miR-199a and ANRIL in diagnosing IBD in adult patients. METHODS: Sixty-seven IBD patients diagnosed clinically, radiologically, endoscopically, and histologically were included in this prospective cohort study. Participants were classified into 3 groups: the UC group (n = 35), the CD group (n = 32), and the control group (n = 30). Demographics, history taking, laboratory characteristics, and treatments were recorded. Tumor necrosis factor α , miR-199a, and ANRIL were measured. RESULTS: The findings suggested that miR-199a and ANRIL might be associated with the occurrence or progression of IBD because both genes were substantially expressed in the peripheral blood of patients with this condition. Receiver-operating characteristic curve analysis indicated that the detection of miR-199a and ANRIL had a predictive sensitivity of 62.9% and 88.6% and a specificity of 70.7% and 96.7% for the occurrence of UC cases, respectively, and a predictive sensitivity of 72.4% and 46.9% and a specificity of 96.7% and 34.7% for the occurrence of CD cases, respectively. CONCLUSIONS: Both miR-199a and ANRIL are abundant in the sera of IBD adult Egyptian patients (UC and CD). Both can represent a noninvasive marker for early disease diagnosis.
This study investigated the relation between tumor necrosis factor α, ANRIL, and miR-199a in inflammatory bowel disease patients to determine the probability of using them as prognostic and diagnostic biomarkers, as well as distinguishing between Crohn's disease and ulcerative colitis patients. Our findings showed that ANRIL and miR-199a can represent noninvasive biomarkers for early disease diagnosis.