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In virotherapy, cancer cells are eradicated via viral infection, replication, and dissemination (oncolysis). BACKGROUND: This study aims to evaluate the oncolytic potential of Newcastle disease virus (NDV) against colon cancer and explore the immune response associated with its therapeutic effects. METHODS: NDV was tested for its oncolytic potential in colon cancer cell lines using MTT assays and apoptosis assessments. Tumor-induced mice were treated with NDV, tumor cell lysate (TCL), or a combination of both. After the euthanasia of murine subjects, an assessment of oncolytic efficacy was performed through flow cytometry analysis of murine blood and tumor tissue, targeting CD83, CD86, CD8, and CD4. An ELISA was also performed to examine interferon-gamma levels, interleukin-4 levels, interleukin-12 levels, and interleukin-10 levels in serum and spleen homogenate. RESULTS: Cell viability was low in HCT116 and HT-29, indicating a cytotoxic effect in the MTT assay. NDV+TCL recorded the highest rate of cell death (56.72%). NDV+TCL had accelerated cell death after 48 h, reaching 58.4%. The flow cytometry analysis of the blood and tumor of mice with induced tumor treated with combined treatment revealed elevated levels of CD83, CD86, CD8, and CD4 (76.3, 66.9, 83.7, and 14.4%, respectively). The ELISA levels of IFN-γ, IL-4, and IL-12 in serum and the spleen homogenate were elevated (107.6 ± 9.25 pg/mL). In contrast, the expression of IL-10 was significantly reduced (1 ± 0.79).
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Human Immunodeficiency Virus (HIV) is a significant threat to public health. HIV genotyping and antiretroviral resistance testing may have contributed to improved non-treated management. Immune markers might assist HIV-1 diagnosis and drug-resistant variant identification. HIV-1 immunogenicity and molecular characteristics of antiretroviral drug resistance are evaluated in 56 treatment-naive HIV patients. DNA sequencing and retroviral resistance testing identified HIV-1 genotypes. 55.4% of patients were susceptible to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) antiretroviral drugs, whereas 44.6% had drug-resistance mutations against at least one antiretroviral drug. 3.6% of cases had PI-resistant mutations, while 30.4% had NRTI-resistant mutations, and 30.4% had NNRTI-resistant mutations. In patients who are susceptible to PI, the mean value of human plasma sCD80 is 2.11 ± 0.65 ng/mL; in patients with mutations, it is 3.93 ± 2.91 ng/mL. Individuals who are susceptible to PI have plasma sCD27 levels of 78.7 ± 63.2 U/mL, whereas individuals who are mutant have levels of 56.5 ± 32.1 U/mL. IP-10's mean value was 363 ± 109.2 pg/mL for the susceptible patients and 429 ± 20.7 pg/mL for the mutated patients. In susceptible patients, the plasma sCD4 level is 0.163 ± 0.229 ng/mL; in mutant patients, it is 0.084 ± 0.012 ng/mL. The data showed a relative relation between immunological parameters such as sCD80, sCD27, sCD4, and IP-10 and mutation for drug resistance.
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Farmacorresistencia Viral , Infecciones por VIH , VIH-1 , Mutación , Humanos , VIH-1/genética , VIH-1/efectos de los fármacos , Arabia Saudita , Masculino , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Infecciones por VIH/inmunología , Infecciones por VIH/genética , Femenino , Adulto , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Genotipo , Adulto JovenRESUMEN
Introduction: Chronic kidney disease (CKD) is a major public health concern in Saudi Arabia. it is pertinent to mention that in the Southwestern region of Saudi Arabia. Hypertension and diabetes mellites are considered the major drivers of CKD. Research has documented worldwide the inappropriate dose adjustments in patients, ranging from 25% to 77%, of drugs requiring dose modifications. Pharmacists are pivotal members of the healthcare team, tasked with addressing issues pertaining to medications. This study aims to unveil pharmacist perspectives on renal dose adjustment in Saudi Arabia an important step in gauging their involvement in promoting healthy behaviours. Method: A cross-sectional study design was conducted from December 2023 to January 2024 among pharmacists working in diverse healthcare settings, including clinical and hospital pharmacies, retail, and community pharmacies who had direct encounters with patients diagnosed with CKD. A validated questionnaire, the Renal Dose Adjustment-13 (RDQ-13) was used for this study. For comparing the knowledge, attitude, and perception scores of pharmacists statistical tests like One-Way ANOVA, and independent t-test; while for factors influencing the knowledge, attitude, and perception scores a multivariate linear regression was performed. The statistical significance level was set at 0.05. Results: A total of 379 pharmacists completed the questionnaire, the knowledge score of pharmacists was 22.06 ± 2.81, while the attitude score was 8.56 ± 2.62 and the practice score was 5.75 ± 2.25. The findings of multivariate linear regression analysis indicated a statistically significant positive association between knowledge score and pharmacist's age while for practice score the findings revealed a statistically negative association between working setting and designation of pharmacists. Conclusion: The pharmacist in Saudi Arabia exhibited a proficient knowledge score of drug dosage adjustment pertinent to renal function while the attitude and practice score was less as compared to the knowledge score.
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This work inspects the utilization of all-polymer solar cells (APSCs) in indoor applications under LED illumination, with a focus on boosting efficiency through simulation-based design. The study employs a SCAPS TCAD device simulator to investigate the performance of APSCs under white LED illumination at 1000 lux, with a power density of 0.305 mW/cm2. Initially, the simulator is validated against experimental results obtained from a fabricated cell utilizing CD1:PBN-21 as an absorber blend and PEDOT:PSS as a hole transportation layer (HTL), where the initial measured efficiency is 16.75%. The simulation study includes an examination of both inverted and conventional cell structures. In the conventional structure, where no electron transportation layer (ETL) is present, various materials are evaluated for their suitability as the HTL. NiO emerges as the most promising HTL material, demonstrating the potential to achieve an efficiency exceeding 27%. Conversely, in the inverted configuration without an HTL, the study explores different ETL materials to engineer the band alignment at the interface. Among the materials investigated, ZnS emerges as the optimal choice, recording an efficiency of approximately 33%. In order to reveal the efficiency limitations of these devices, the interface and bulk defects are concurrently investigated. The findings of this study underscore the significance of careful material selection and structural design in optimizing the performance of APSCs for indoor applications.
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Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.
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Biomarcadores de Tumor , Miembro 14 de Receptores del Factor de Necrosis Tumoral , Humanos , Miembro 14 de Receptores del Factor de Necrosis Tumoral/metabolismo , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Adulto , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Células K562 , Células HEK293 , Proliferación Celular , Anciano , Línea Celular Tumoral , Adulto Joven , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunologíaRESUMEN
[This retracts the article DOI: 10.7759/cureus.19418.].
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Background and Aim: Salinomycin sodium, a licensed coccidiostat in rabbits, is used for fattening at a dose of 20-25 mg/kg. Salinomycin toxicity may arise from many risk factors (e.g., overdosage or use in non-target animal species). Silymarin extracted from milk thistle has antioxidant, anti-inflammatory, and antiviral properties. This study aimed to investigate the adverse impacts of oral administration of salinomycin for 28 consecutive days and how to reduce its risks and side effects by administering silymarin. Materials and Methods: Eighty-four male New Zealand White bucks (1.750-2.000 kg) were randomly divided into seven groups (12 each). Group one was the control. Groups two and three were administered salinomycin orally (doses of 20 and 40 mg/kg ration). Group four was administered salinomycin (20 mg/kg ration) and silymarin (6.5 mg/kg body weight [BW]). Group five received salinomycin (40 mg/kg ration) and silymarin (13 mg/kg BW). Groups six and seven were administered silymarin at doses of 6.5 and 13 mg/kg BW. Rabbits were euthanized and slaughtered on day 29 using the Halal method. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, total proteins, albumin, total cholesterol, and high- and low-density lipoprotein (HDL and LDL) were analyzed in serum. Glutathione (GSH), superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were estimated in the liver. A histopathological investigation was performed on the liver and kidney. Results: The MDA activity, AST, ALT, total protein, albumin, total cholesterol, triglyceride, LDL, urea, and creatinine values were significantly elevated in groups two and three. The GSH, catalase, SOD, and HDL were significantly lower in these groups than in the control group. There were moderate pathologic changes in the liver and kidney of the third group. However, the results of the fourth and fifth groups improved more than those of the second and third groups. The results of the sixth and seventh groups were nearly the same as those of the control group. Conclusion: Salinomycin toxicity was caused by oxidative damage because of reactive oxygen species formation. Silymarin (6.5 or 13 mg/kg BW) tends to prevent and treat accidental toxicity. However, the high dose of silymarin (13 mg/kg BW) had more renal and hepatoprotective capacities.
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[This retracts the article DOI: 10.1007/s10772-021-09878-0.].
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BACKGROUND: Titanium dioxide nanoparticles (TiO2-NPs) are widely utilized in medicine and industry; however, their safety in biological organisms is still unclear. In this study, we determined the bioactive constitutes of thyme essential oil (TEO) and utilized the nanoemulsion technique to improve its protective efficiency against oxidative stress, genotoxicity, and DNA damage of biosynthesized titanium dioxide nanoparticles (TiO2-NPs). METHODS: TEO nanoemulsion (TEON) was prepared using whey protein isolate (WPI). Sixty male Sprague-Dawley rats were divided into six groups and treated orally for 21 days including the control group, TEO, or TEON- treated groups (5 mg/kg b.w), TiO2-NPs-treated group (50 mg/kg b.w) and the groups received TiO2-NPs plus TEO or TEON. Blood and tissues samples were collected for different assays. RESULTS: The GC-MS analysis identified 17 bioactive compounds in TEO and thymol and carvacrol were the major compounds. TEON was irregular with average particles size of 230 ± 3.7 nm and ζ-potential of -24.17 mV. However, TiO2-NPs showed a polygonal shape with an average size of 50 ± 2.4 nm and ζ-potential of -30.44 mV. Animals that received TiO2-NPs showed severe disturbances in liver and kidney indices, lipid profile, oxidant/antioxidant indices, inflammatory cytokines, gene expressions, increased DNA damage, and pathological changes in hepatic tissue. Both TEO and TEON showed potential protection against these hazards and TEON was more effective than TEO. CONCLUSION: The nanoemulsion of TEO enhances the oil bioactivity, improves its antioxidant characteristics, and protects against oxidative damage and genotoxicity of TiO2-NPs.
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Nanopartículas , Aceites Volátiles , Thymus (Planta) , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Daño del ADN , Expresión Génica , Masculino , Aceites Volátiles/farmacología , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Thymus (Planta)/metabolismo , Titanio/farmacologíaRESUMEN
Background: The coronavirus pandemic (COVID-19) resulted in disruption in the traditional teaching methods and lead to a wider adoption of virtual teaching. However, there is a lack of comparative studies regarding the use of either or the mixed mode for teaching radiology to undergraduate students. Objective: This study aimed to determine the barriers, performance, and overall satisfaction of undergraduate medical students and instructors undertaking virtual and traditional radiology learning across Saudi Arabia. Methodology: This cross-sectional questionnaire study included undergraduate students and instructors from across Saudi Arabia who had undertaken radiology either traditionally, through E-learning, or both in the 2019-20 academic year. The questionnaire elicited information regarding attendance, teaching methods, difficulties, knowledge acquisition, and satisfaction. Association between variables was assessed using Chi-square, in addition to a univariate analysis. Results: A total of 404 undergraduate students from 28 universities of Saudi Arabia responded, in addition to 20 instructors. Students preferred E-learning for the quality of the course and the time and effort spent as well as obtained higher grades than those in traditional learning. Traditional education was favored over E-learning for clarity of instructors' voice, ease of understanding image description by the instructor, and lack of technical barriers such as poor Internet connection. The form of education was significantly correlated with grades obtained (P < 0.001) but not with overall satisfaction (P = 0.067). The majority of the instructors (60%) considered E-learning to be helpful in balancing their workload and teaching responsibilities (P = 0.029) and would recommend it as a standard teaching method for radiology (85%). Conclusion: E-learning has potential advantages over traditional learning for teaching radiology to undergraduate medical students. However, further optimization is required to overcome the current deficiencies of this mode.
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Researchers and scientists have been conducting plenty of research on COVID-19 since its outbreak. Healthcare professionals, laboratory technicians, and front-line workers like sanitary workers, data collectors are putting tremendous efforts to avoid the prevalence of the COVID-19 pandemic. Currently, the reverse transcription polymerase chain reaction (RT-PCR) testing strategy determines the COVID-19 virus. This RT-PCR processing is more expensive and induces violation of social distancing rules, and time-consuming. Therefore, this research work introduces generative adversarial network deep learning for quickly detect COVID-19 from speech signals. This proposed system consists of two stages, pre-processing and classification. This work uses the least mean square (LMS) filter algorithm to remove the noise or artifacts from input speech signals. After removing the noise, the proposed generative adversarial network classification method analyses the mel-frequency cepstral coefficients features and classifies the COVID-19 signals and non-COVID-19 signals. The results show a more prominent correlation of MFCCs with various COVID-19 cough and breathing sounds, while the sound is more robust between COVID-19 and non-COVID-19 models. As compared with the existing Artificial Neural Network, Convolutional Neural Network, and Recurrent Neural Network, the proposed GAN method obtains the best result. The precision, recall, accuracy, and F-measure of the proposed GAN are 96.54%, 96.15%, 98.56%, and 0.96, respectively.
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Musculoskeletal disorders represent a major public health problem and they are frequently managed in primary care centers. Shoulder pain is a frequent musculoskeletal complaint and it can result from intrinsic disorders of the shoulder or referred pain. We present the case of a 24-year-old woman who presented to the family medicine clinic complaining of left shoulder pain for three months duration. The pain was not associated with numbness or weakness. There was no history of preceding trauma. The initial diagnosis was supraspinatus tendinosis. The patient was prescribed oral analgesics and was advised to undergo multiple physiotherapy sessions. Later, the patient presented to the clinic again and reported she did not have any improvement in her symptoms. The patient was referred to the orthopedic clinic for further evaluation and management. The patient underwent a frontal radiograph of the chest which demonstrated a well-defined opacity located in the apex of the left lung. A computed tomography scan of the chest demonstrated the presence of erosion to the vertebral body raising the suspicion for a neurogenic tumor as was later supported by magnetic resonance imaging. The patient underwent video-assisted thoracotomy with brachial plexus exploration. Complete resection of the tumor was achieved with no complications. The present case highlights those common musculoskeletal complaints, such as shoulder pain, which could indicate underlying non-orthopedic pathology.
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One of the most important challenges in the design of the piezoelectric energy harvester is its narrow bandwidth. Most of the input vibration sources are exposed to frequency variation during their operation. The piezoelectric energy harvester's narrow bandwidth makes it difficult for the harvester to track the variations of the input vibration source frequency. Thus, the harvester's output power and overall performance is expected to decline from the designed value. This current study aims to solve the problem of the piezoelectric energy harvester's narrow bandwidth. The main objective is to achieve bandwidth broadening which is carried out by segmenting the piezoelectric material of the energy harvester into n segments; where n could be more than one. Three arrays with two, four, and six beams are shaped with two piezoelectric segments. The effect of changing the length of the piezoelectric material segment on the resonant frequency, output power, and bandwidth, as well as the frequency response is investigated. The proposed piezoelectric energy harvesters were implemented utilizing a finite element method (FEM) simulation in a MATLAB environment. The results show that increasing the number of array beams increases the output power and bandwidth. For the three-beam arrays, at n equals 2, 6 mW output power and a 9 Hz bandwidth were obtained. Moreover, the bandwidth of such arrays covered around 5% deviation from its resonant frequency. All structures were designed to operate as a steel wheel safety sensor which could be used in train tracks.
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This study of selected plants of the Rutaceae family was carried out to investigate their phenolic content, antioxidant activity, and the in vitro inhibitory potential of extracted phenolics towards enzymes relevant for hyperglycemia and hypertension. The phenolic content, antioxidant activity and phenolic extract-mediated inhibitory activities for α-glucosidase and α-amylase were evaluated by spectrophotometry. The content of individual phenolics and the angiotensin I-converting enzyme (ACE) inhibitory activity of the phenolic extracts were evaluated by LC/MS-MS and RP-HPLC methods, respectively. A higher percentage of free phenolic content was seen for all the selected plants of the Rutaceae family (85.43-92.82% of the total phenolic content) than of the bound form (7.18-14.57% of total phenolic content). The major predominant bound phenolic in lemon and red blood orange was hesperidin. The major predominant bound phenolic in pummelo, shamouti and clementine was ferulic acid. The highest ACE and α-glucosidase inhibitory activity of the extracted phenolics from lemon was associated with free phenolic extracts obtained at 30 °C with values of 100% inhibition. Red blood orange free phenolic extract (30 °C) elicited the highest α-amylase inhibition activity (32.3%). In contrast, extracted bound phenolics after acid and base hydrolysis from all selected plants from the Citrus species were shown to induce activation of the ACE and α-amylase enzymes.
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Antihipertensivos/química , Antioxidantes/química , Citrus/química , Hipoglucemiantes/química , Fenoles/química , Extractos Vegetales/química , Antihipertensivos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Frutas/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Fenoles/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/química , alfa-Glucosidasas/químicaRESUMEN
Europium (III) with different concentrations (0.2, 0.4 and 0.8 %)-TiO(2) doped silica composite systems were sensitized by sol-gel method. Different spectroscopic and microscopic tools characterized the composites. The Europium ion incorporated into the liquid silica-titania solution acts as red light emission center in the luminescent materials. This luminescent nano composite pigment has great potential of application in preparing luminescent ink. Inkjet printer loaded with the prepared ink to show its potential usage as tagging material performed the printing test on a white paper.
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A Saudi Arabian family is described in which there were 2 siblings with typical features of cerebral xanthomatosis CTX including premature cataracts, xanthomata of the Achilles tendons, neuro-psychiatric disturbances, and atherosclerosis. The 2 patients were homozygous for a point mutation in the mitochondrial 27-hydroxylase gene CYP27A1, OMIM 606530 located in the splice site of intron 6, where G was exchanged for A IVS6+1G>A. Their parents were cousins, 5 siblings were healthy, 2 were heterozygous for the mutation, and one showed the wild-type genotype. The father was heterozygous for the mutation, while the other family members were not tested. The progress of the 2 CTX patients over 14 years is described; firstly when they were receiving treatment with chenodeoxycholic acid; when this medication was not available, and later when it was restored. A hereditary hyperlipidemia was also present in this family. It is suggested that when this occurs with CTX, a more serious illness results that merits more aggressive dual therapy.