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OBJECTIVE: To verify the discriminative power of irisin in osteoporosis patients. METHODS: The comparative case-control study was conducted at the University Teaching Hospital, Baghdad, Iraq, from March 2020 to June 2021 after approval from the ethics review committee of the College of Medicine, Mustansiriyah University, Baghdad, and comprised post-menopausal women. After being scanned by dual-energy X-ray absorptiometer, the subjects were divided into groups based on T-scores; healthy controls with T-score > -1 in group 1, and osteoporosis patients with T-score ≤-2.5 in group 2. Participants' sera were tested for Irisin, 25- hydroxy vitamin D, and carboxyl-terminal telopeptides of type I collagen levels. T-score and bone mineral density were recorded as radiological markers. Correlation of irisin was determined with T-score and bone mineral density, cut-off value for serum irisin was worked out for osteoporosis prediction. Data was analysed using Medcalic 17. RESULTS: Of the 142 women, 71(50%) were in group 1 with mean age 58.4±3.5 years, and 71(50%) were in group 2 with mean age 58.7±3.4 years (p=0.87). Levels of irisin, 25-hydroxy vitamin D, carboxyl-terminal telopeptides of type I collagen, bone mineral density and T-scores were significant between the groups (p<0.001). Serum irisin correlated directly with bone mineral density (r=0.97, p<0.001) and inversely with T-score (r= -0.95, p<0.001). The cut-off value of serum irisin was 31.4ng/ml with 84% sensitivity and 100% specificity (p<0.001). CONCLUSIONS: Strong serum irisin correlation to osteoporosis radiological markers and its good discrimination of osteoporosis implied its utility as a good serological marker of osteoporosis.
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Absorciometría de Fotón , Biomarcadores , Densidad Ósea , Fibronectinas , Osteoporosis Posmenopáusica , Vitamina D , Humanos , Femenino , Fibronectinas/sangre , Persona de Mediana Edad , Estudios de Casos y Controles , Absorciometría de Fotón/métodos , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/diagnóstico , Vitamina D/sangre , Vitamina D/análogos & derivados , Biomarcadores/sangre , Colágeno Tipo I/sangre , Péptidos/sangreRESUMEN
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and the integration of CAR T cells with other therapeutic modalities. This comprehensive analysis underscores the synergistic potential of these strategies to enhance the safety, efficacy, and accessibility of CAR T-cell therapies, providing a forward-looking perspective on their evolutionary trajectory in cancer treatment.
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Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Biología Sintética , Microambiente Tumoral , Humanos , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/economía , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Neoplasias/terapia , Neoplasias/inmunología , Biología Sintética/métodos , Microambiente Tumoral/inmunología , Animales , Linfocitos T/inmunología , Linfocitos T/trasplante , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
BACKGROUND: Prodigiosin is a naturally occurring compound produced by various bacteria, including Serratia marcescens. It is known for its diverse biological properties. The present study was conducted to extract and purify prodigiosin from Serratia marcescens and investigate its anticancer and immunomodulatory activities. METHODS: S. presence was isolated from soil samples and characterized. Different solvents were used to extract prodigiosin from Serratia marcescens. The cytotoxic activity of prodigiosin was tested against human rhabdomyosarcoma (RD), rat embryo fibroblasts (REF), and human breast cancer MDA-MB-231 (MDA) epithelial cell lines. Albino mice were divided into six groups: Negative control (normal saline); positive control (injected with 100 µ l of Serratia marcesence); groups A-D were injected with 100 µ l of prodigiosin (1, 3, 6, and 9 µ g/mouse, respectively). After 14 days of treatment, whole blood samples were collected for immunomodulatory analysis. RESULTS: The study found that the highest yield of prodigiosin (65-230 mg/l) was obtained with methanol as the extraction solvent. Prodigiosin had a cytotoxic effect on cancer cells, particularly against MDA epithelial cells. However, it did not have a cytotoxic effect on normal cells. Immunological analysis revealed significant differences (p ≤ 0.01) in absolute neutrophil counts between the positive control and prodigiosin-treated groups, with the highest value in group C and the lowest in group A. Immunological analysis showed significant differences in neutrophil counts, IL-4, and IL-10 levels between prodigiosin-treated groups and the control group. CONCLUSION: Serratia marcescens prodigiosin showed cytotoxic effects on cancer cells and boosted IL-10 and IL-4 serum levels, acting as an immunomodulator.
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Antineoplásicos , Prodigiosina , Serratia marcescens , Prodigiosina/farmacología , Ratones , Animales , Humanos , Ratas , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Factores Inmunológicos/farmacología , Femenino , Células Tumorales Cultivadas , Agentes Inmunomoduladores/farmacologíaRESUMEN
Objective: The purpose of this study was to investigate the technical feasibility of integrating the quantitative maps available from SyntheticMR into the head and neck adaptive radiation oncology workflow. While SyntheticMR has been investigated for diagnostic applications, no studies have investigated its feasibility and potential for MR-Simulation or MR-Linac workflow. Demonstrating the feasibility of using this technique will facilitate rapid quantitative biomarker extraction which can be leveraged to guide adaptive radiation therapy decision making. Approach: Two phantoms, two healthy volunteers, and one patient were scanned using SyntheticMR on the MR-Simulation and MR-Linac devices with scan times between four to six minutes. Images in phantoms and volunteers were conducted in a test/retest protocol. The correlation between measured and reference quantitative T1, T2, and PD values were determined across clinical ranges in the phantom. Distortion was also studied. Contours of head and neck organs-at-risk (OAR) were drawn and applied to extract T1, T2, and PD. These values were plotted against each other, clusters were computed, and their separability significance was determined to evaluate SyntheticMR for differentiating tumor and normal tissue. Main Results: The Lin's Concordance Correlation Coefficient between the measured and phantom reference values was above 0.98 for both the MR-Sim and MR-Linac. No significant levels of distortion were measured. The mean bias between the measured and phantom reference values across repeated scans was below 4% for T1, 7% for T2, and 4% for PD for both the MR-Sim and MR-Linac. For T1 vs. T2 and T1 vs. PD, the GTV contour exhibited perfect purity against neighboring OARs while being 0.7 for T2 vs. PD. All cluster significance levels between the GTV and the nearest OAR, the tongue, using the SigClust method was p < 0.001. Significance: The technical feasibility of SyntheticMR was confirmed. Application of this technique to the head and neck adaptive radiation therapy workflow can enrich the current quantitative biomarker landscape.
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OBJECTIVES: The current understanding of survival prediction of lung transplant (LTx) patients with systemic sclerosis (SSc) is limited. This study aims to identify novel image features from preoperative chest CT scans associated with post-LTx survival in SSc patients and integrate them into comprehensive prediction models. MATERIALS AND METHODS: We conducted a retrospective study based on a cohort of SSc patients with demographic information, clinical data, and preoperative chest CT scans who underwent LTx between 2004 and 2020. This cohort consists of 102 patients (mean age, 50 years ± 10, 61% (62/102) females). Five CT-derived body composition features (bone, skeletal muscle, visceral, subcutaneous, and intramuscular adipose tissues) and three CT-derived cardiopulmonary features (heart, arteries, and veins) were automatically computed using 3-D convolutional neural networks. Cox regression was used to identify post-LTx survival factors, generate composite prediction models, and stratify patients based on mortality risk. Model performance was assessed using the area under the receiver operating characteristics curve (ROC-AUC). RESULTS: Muscle mass ratio, bone density, artery-vein volume ratio, muscle volume, and heart volume ratio computed from CT images were significantly associated with post-LTx survival. Models using only CT-derived features outperformed all state-of-the-art clinical models in predicting post-LTx survival. The addition of CT-derived features improved the performance of traditional models at 1-year, 3-year, and 5-year survival prediction with maximum AUC scores of 0.77 (0.67-0.86), 0.85 (0.77-0.93), and 0.90 (95% CI: 0.83-0.97), respectively. CONCLUSION: The integration of CT-derived features with demographic and clinical features can significantly improve t post-LTx survival prediction and identify high-risk SSc patients. KEY POINTS: Question What CT features can predict post-lung-transplant survival for SSc patients? Finding CT body composition features such as muscle mass, bone density, and cardiopulmonary volumes significantly predict survival. Clinical relevance Our individualized risk assessment tool can better guide clinicians in choosing and managing patients requiring lung transplant for systemic sclerosis.
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Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory-like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In the current study, CIML NK cells demonstrated superior antitumor responses against a panel of EOC cell lines, increased expression of activation receptors, and up-regulation of genes involved in cell cycle/proliferation and down-regulation of inhibitory/suppressive genes. CIML NK cells transduced with a chimeric antigen receptor (CAR) targeting the membrane-proximal domain of mesothelin (MSLN) further improved the antitumor responses against MSLN-expressing EOC cells and patient-derived xenograft tumor cells. CAR arming of the CIML NK cells subtanstially reduced their dysfunction in patient-derived ascites fluid with transcriptomic changes related to altered metabolism and tonic signaling as potential mechanisms. Lastly, the adoptive transfer of MSLN-CAR CIML NK cells demonstrated remarkable inhibition of tumor growth and prevented metastatic spread in xenograft mice, supporting their potential as an effective therapeutic strategy in EOC.
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Células Asesinas Naturales , Mesotelina , Neoplasias Ováricas , Animales , Femenino , Humanos , Ratones , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/inmunología , Carcinoma Epitelial de Ovario/terapia , Línea Celular Tumoral , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Memoria Inmunológica , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/terapia , Dominios Proteicos , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Isochoric (constant-volume or volumetrically confined) vitrification has shown potential as an alternative cryopreservation-by-vitrification technique, but the complex processes at play within the chamber are yet poorly characterized, and recent investigations have prompted significant debate around whether a truly isochoric vitrification process (in which the liquid remains completely confined by solid boundaries) is indeed feasible. Based on a recent thermomechanical simulation of a high-concentration Me2SO solution, Solanki and Rabin (Cryobiology, 2023, 111, 9-15.) argue that isochoric vitrification is not feasible, because differential thermal contraction of the solution and container will necessarily drive generation of a cavity, corrupting the rigid confinement of the liquid. Here, we provide direct experimental evidence to the contrary, demonstrating cavity-free isochoric vitrification of a â¼3.5 M vitrification solution by combined isochoric pressure measurement (IPM) and photon-counting x-ray computed tomography (PC-CT). We hypothesize that the absence of a cavity is due to the minimal thermal contraction of the solution, which we support with additional volumetric analysis of the PC-CT reconstructions. In total, this study provides experimental evidence both demonstrating the feasibility of isochoric vitrification and highlighting the potential of designing vitrification solutions that exhibit minimal thermal contraction.
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Criopreservación , Fotones , Tomografía Computarizada por Rayos X , Vitrificación , Criopreservación/métodos , Tomografía Computarizada por Rayos X/métodos , Presión , HieloRESUMEN
To ensure the structural integrity of concrete and prevent unanticipated fracturing, real-time monitoring of early-age concrete's strength development is essential, mainly through advanced techniques such as nano-enhanced sensors. The piezoelectric-based electro-mechanical impedance (EMI) method with nano-enhanced sensors is emerging as a practical solution for such monitoring requirements. This study presents a strength estimation method based on Non-Destructive Testing (NDT) Techniques and Long Short-Term Memory (LSTM) and artificial neural networks (ANNs) as hybrid (NDT-LSTMs-ANN), including several types of concrete strength-related agents. Input data includes water-to-cement rate, temperature, curing time, and maturity based on interior temperature, allowing experimentally monitoring the development of concrete strength from the early steps of hydration and casting to the last stages of hardening 28 days after the casting. The study investigated the impact of various factors on concrete strength development, utilizing a cutting-edge approach that combines traditional models with nano-enhanced piezoelectric sensors and NDT-LSTMs-ANN enhanced with nanotechnology. The results demonstrate that the hybrid provides highly accurate concrete strength estimation for construction safety and efficiency. Adopting the piezoelectric-based EMI technique with these advanced sensors offers a viable and effective monitoring solution, presenting a significant leap forward for the construction industry's structural health monitoring practices.
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Materiales de Construcción , Impedancia Eléctrica , Aprendizaje Automático , Redes Neurales de la Computación , Materiales de Construcción/análisis , Nanotecnología/instrumentación , Nanotecnología/métodos , Ensayo de Materiales/métodosAsunto(s)
Epigénesis Genética , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Linfocitos T , Humanos , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Inmunoterapia Adoptiva/métodosRESUMEN
BACKGROUND: To accelerate the translation of novel immunotherapeutic treatment approaches, the development of analytic methods to assess their efficacy at early in vitro stages is necessary. Using a droplet-based microfluidic platform, we have established a method for multiparameter quantifiable phenotypic and genomic observations of immunotherapies. Chimeric antigen receptor (CAR) natural killer (NK) cells are of increased interest in the current immunotherapy landscape and thus provide an optimal model for evaluating our novel methodology. METHODS: For this approach, NK cells transduced with a CD19 CAR were compared with non-transduced NK cells in their ability to kill a lymphoma cell line. Using our microfluidic platform, we were able to quantify the increase in cytotoxicity and synaptic contact formation of CAR NK cells over non-transduced NK cells. We then optimized our droplet sorter and successfully used it to separate NK cells based on target cell killing to perform transcriptomic analyses. RESULTS: Our data revealed expected improvement in cytotoxicity with the CD19 CAR but more importantly, provided unique insights into the factors involved in the cytotoxic mechanisms of CAR NK cells. This demonstrates a novel, improved system for accelerating the pre-clinical screening of future immunotherapy treatments. CONCLUSIONS: This study provides a new potential approach for enhanced early screening of immunotherapies to improve their development, with a highly relevant cell model to demonstrate. Additionally, our validation studies provided some potential insights into transcriptomic determinants influencing CAR NK cytotoxicity.
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Células Asesinas Naturales , Receptores Quiméricos de Antígenos , Análisis de la Célula Individual , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Humanos , Análisis de la Célula Individual/métodos , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Inmunoterapia Adoptiva/métodos , Fenotipo , Citotoxicidad Inmunológica , Genotipo , Línea Celular TumoralRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia impetiginosa (Bignoniaceae) was traditionally used for memory enhancement and central nervous system (CNS) stimulation. AIM OF THE STUDY: This study aims to create a metabolic profile of the ethyl acetate fraction of T. impetiginosa (TEF) and investigate for the first time its neuroprotective potential on cyclophosphamide (CP)-induced chemobrain, validating its traditional use. MATERIALS AND METHODS: Metabolite profiling of TEF was performed using Liquid Chromatography coupled with Quadrupole Time of Flight-Mass/Mass Spectrometry (LC-qTOF-MS/MS). For the in vivo study, CP (200 mg/kg, i.p.) was administered to induce cognitive impairment in rats; TEF (30 mg/kg, p.o.) was administered throughout the 14 days of the experiment to assess its role in mitigating CP-induced neuronal deficits. Behavioral tests including locomotor, Y-maze, and passive avoidance tests were conducted. Additionally, biochemical markers such as reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and caspase-3 immunoexpression were assessed in the hippocampus area. RESULTS: Forty-four phytoconstituents were tentatively identified in TEF, mainly iridoids and organic acids. TEF showed significant memory enhancement as evidenced by the increase in step-through latency in the passive avoidance test by 1.5 folds and the increase in sequence alternation percentage (SAP) in the Y-maze test by 67.3%, as compared to CP-group. Moreover, it showed pronounced antioxidant and anti-inflammatory potentials evidenced by the significant elevation in reduced glutathione (GSH) levels by 80% and a pronounced decline in MDA and TNF-α levels by 24% and 45%, respectively relative to the CP group. TEF treatment restored normal hippocampal histological features and attenuated apoptotic caspase-3 expression by 70% compared to the CP group. CONCLUSIONS: TEF can act as a promising natural scaffold in managing the chemobrain induced by CP in cancer patients.
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Fármacos Neuroprotectores , Extractos Vegetales , Hojas de la Planta , Espectrometría de Masas en Tándem , Animales , Fármacos Neuroprotectores/farmacología , Espectrometría de Masas en Tándem/métodos , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Ratas , Cromatografía Liquida/métodos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/análisis , Ratas Wistar , Ciclofosfamida/toxicidad , Aprendizaje por Laberinto/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Glutatión/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.
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Cymbopogon , Agua Potable , Cálculos Renales , Polietilenglicoles , Polietileneimina , Urolitiasis , Animales , Ratas , Petroselinum , Cloruro de Amonio , Goma Arábiga , Emulsiones , Catalasa , Magnesio , Nanogeles , Urolitiasis/inducido químicamente , Urolitiasis/tratamiento farmacológico , Urolitiasis/prevención & control , Semillas , Antioxidantes/uso terapéutico , Etanol , Glutatión , Oxalatos , Glicoles de Etileno , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
The exquisite balance between cellular prosurvival and death pathways is extremely necessary for homeostasis. Different forms of programmed cell death have been widely studied and reported such as apoptosis, necroptosis, pyroptosis, and autophagy. Autophagy is a catabolic process important for normal cellular functioning. The main aim of this machinery is to degrade the misfolded or damaged proteins, unuseful organelles, and pathogens, which invade the cells, thereby maintaining cellular homeostasis and assuring the regular renewal of cell components. This prosurvival function of autophagy highlights its importance in many human diseases, as the disturbance of this tightly organized process ultimately causes detrimental effects. Interestingly, neurons are particularly susceptible to damage upon the presence of any alteration in the basal level of the autophagic activity; this could be due to their high metabolic demand, post-mitotic nature, and the contribution of autophagy in the different fundamental functions of neurons. Herein, we have reported the role of autophagy in different CNS disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and epilepsy, besides the pharmacological agents targeting autophagy. Due to the significant contribution of autophagy in the pathogenesis of many diseases, it is crucial to develop effective methods to detect this dynamic process. In this chapter, we have summarized the most frequently employed techniques in studying and detecting autophagy including electron microscopy, fluorescence microscopy, Western blotting, intracellular protein degradation, and sequestration assay.
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Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.
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Antineoplásicos , Neoplasias del Colon , Ajo , Plantas Medicinales , Masculino , Humanos , Extractos Vegetales/química , Estudios Prospectivos , Ácidos Sulfínicos/química , Disulfuros , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Ajo/químicaRESUMEN
OBJECTIVES: To investigate the relationship between statin use and coronavirus disease-19 (COVID-19) severity. METHODS: This was a retrospective study of adult patients with confirmed COVID-19 who were hospitalized at Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia. The study was carried out from July - September 2020. Antecedent statin use was evaluated using medication information available in the electronic medical records. RESULTS: In this retrospective study, we collected data from 689 patients hospitalized with COVID-19. Among the patients, 56.2% of them were non-Saudi and 67.3% were males. The mean age of the patients was 53.7 years. The most common comorbidities among patients with COVID-19 at admission were hypertension (65.2%) and diabetes mellitus (65%). Among these patients, 155 (22.5%) patients received statins during hospitalization and 79.7% of them received corticosteroids. Receiving statins significantly increased the risk of intensive care unit's admission by 1.64 times, intubation by 1.76 times, developing complications by 2.48 times, and mortality by 3.16 times. CONCLUSION: Statins are associated with a higher risk of mortality and morbidity among patients hospitalized for COVID-19.
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COVID-19 , Diabetes Mellitus , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Adulto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Arabia Saudita/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiologíaRESUMEN
The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.
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Gastritis , Úlcera Gástrica , Óxido de Zinc , Ratas , Animales , Etanol , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Gastritis/inducido químicamente , Gastritis/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patologíaRESUMEN
BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.
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Tasa de Filtración Glomerular , Inmunosupresores , Humanos , Masculino , Niño , Femenino , Estudios Retrospectivos , Adolescente , Inmunosupresores/uso terapéutico , Preescolar , Pronóstico , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Estudios de Seguimiento , Terapia de Inmunosupresión/métodos , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/complicaciones , Vasculitis por IgA/diagnóstico , Resultado del Tratamiento , Vasculitis/tratamiento farmacológicoRESUMEN
A novel series of triazole-benzohydrazone hybrids was efficiently designed and synthesized as antiproliferative agents, targeting different kinases. All compounds were screened via the National Cancer Institute (NCI) against 60 cancer cell lines, where compounds 16, 17, and 18 exhibited growth inhibition percent (GI%) of various leukemia subpanels with values of 70.33%, 64.13%, and 76.03%, respectively. Compound 18 showed broad-spectrum antiproliferative efficacy toward most cancer cells, with outstanding potency regarding melanoma (MALME-3M GI% = 101.82%) and breast cancer cell lines (MCF7 GI% = 85.87%), while proving safe toward the WI-38 normal cell line, compared to doxorubicin. Multikinase investigation including vascular endothelial growth factor receptor 2 (VEGFR-2), mesenchymal epithelial transition factor (c-Met), proto-oncogene B-Raf, mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, and phosphoinositide 3-kinase was accomplished to reveal its plausible mechanism of action, giving the ultimate potency against both VEGFR-2 and c-Met with IC50 values of 0.055 and 0.042 µM, respectively, while displaying moderate to good inhibition concerning the remaining kinases. DNA binding capability was excluded using the methyl green colorimetric assay. Further, it exhibited both early and late apoptotic induction by about 16- and 9.4-fold over the control, respectively, triggering cell cycle arrest in the G2/M phase. Physicochemical properties and bioavailability radar plot inferred drug-likeness characteristics for compound 18. The molecular docking study assessed the binding pattern with the active sites of c-Met and VEGFR-2.