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Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer. Both in vitro and in vivo anti-inflammatory activities of the synthesized compounds were assessed relative to the positive standards: celecoxib and indomethacin. The in vitro enzymatic and transcription inhibitory actions of all the synthesized compounds were tested against cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1), and 5-lipoxygenase (LOX) and the in vivo gene expression of Interleukin-1, interleukin 10, and Tumor Necrosis Factor-α (TNF-α) were determined. The IC50 against COX-1 and COX-2 enzymes obtained by the immunoassay test revealed promising activities of sixteen compounds with selectivity indices higher than 100-fold COX-2 selectivity. Out of those, four compounds revealed selectivity indices comparable to celecoxib as a reference drug. Furthermore, all the tested compounds inhibited LOX with an IC50 in the range of 1.59-3.11 µM superior to that of the reference drug used; zileuton (IC50 = 3.50 µM). Consequently, these results highlight the promising LOX inhibitory activity of the tested compounds. The obtained in vivo paw edema results showed high inhibitory percentage for the compounds 9a, 9b, and 11a with the significant lower TNF-α relative mRNA expression for compounds 5a, 5d, 9a, 9b, 12d, and 12e. Finally, in silico docking of the most active compounds (5b, 5d, 9a, 9b) against COX2 enzymes presented an acceptable justification of the obtained in vitro inhibitory activities. As a conclusion, Compounds 5b, 5d, 9a, 9b, and 11b showed promising results and thus deserves further investigation.
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Antiinflamatorios , Ciclooxigenasa 2 , Edema , Inhibidores de la Lipooxigenasa , Quinonas , Animales , Inhibidores de la Lipooxigenasa/farmacología , Ratas , Ciclooxigenasa 2/metabolismo , Edema/tratamiento farmacológico , Quinonas/farmacología , Antiinflamatorios/farmacología , Masculino , Inhibidores de la Ciclooxigenasa/farmacología , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular/métodos , Araquidonato 5-Lipooxigenasa/metabolismo , Ratas Wistar , Ciclooxigenasa 1/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , CarrageninaRESUMEN
Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement: The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.
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As a new approach to the management of inflammatory disorders, a series of chromone-based derivatives containing a (carbamate)hydrazone moiety was designed and synthesized. The compounds were assessed for their ability to inhibit COX-1/2, 15-LOX, and mPGES-1, as a combination that should effectively impede the arachidonate pathway. Results revealed that the benzylcarbazates (2a-c) demonstrated two-digit nanomolar COX-2 inhibitory activities with reasonable selectivity indices. They also showed appreciable 15-LOX inhibition, in comparison to quercetin. Further testing of these compounds for mPGES-1 inhibition displayed promising activities. Intriguingly, compounds 2a-c were capable of suppressing edema in the formalin-induced rat paw edema assay. They exhibited an acceptable gastrointestinal safety profile regarding ulcerogenic liabilities in gross and histopathological examinations. Additionally, upon treatment with the test compounds, the expression of the anti-inflammatory cytokine IL-10 was elevated, whereas that of TNF-α, iNOS, IL-1ß, and COX-2 were downregulated in LPS-challenged RAW264.7 macrophages. Docking experiments into the three enzymes showed interesting binding profiles and affinities, further substantiating their biological activities. Their in silico physicochemical and pharmacokinetic parameters were advantageous.
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Antiinflamatorios , Inhibidores de la Lipooxigenasa , Ratas , Animales , Ciclooxigenasa 2/metabolismo , Inhibidores de la Lipooxigenasa/química , Ciclooxigenasa 1/metabolismo , Antiinflamatorios/farmacología , Ácidos Araquidónicos , Edema/inducido químicamente , Edema/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Araquidonato 5-Lipooxigenasa/metabolismo , Relación Estructura-ActividadRESUMEN
Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis: The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination: Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.
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Objective: The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018. Methods: Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021. Results: The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33). Conclusions: e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network. Significance statement Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.
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To provide an overview of the I-CAH Registry. Following the successful roll-out of the I-DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I-CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I-CAH Registry are important tools for all stakeholders involved in the care of people with CAH.
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Cardiovascular complications of diabetes and obesity remain a major cause for morbidity and mortality worldwide. Despite significant advances in the pharmacotherapy of metabolic disease, the available approaches do not prevent or slow the progression of complications. Moreover, a majority of patients present with significant vascular involvement at early stages of dysfunction prior to overt metabolic changes. The lack of disease-modifying therapies affects millions of patients globally, causing a massive economic burden due to these complications. Significantly, adipose tissue inflammation was implicated in the pathogenesis of metabolic syndrome, diabetes, and obesity. Specifically, perivascular adipose tissue (PVAT) and perirenal adipose tissue (PRAT) depots influence cardiovascular and renal structure and function. Accumulating evidence implicates localized PVAT/PRAT inflammation as the earliest response to metabolic impairment leading to cardiorenal dysfunction. Increased mitochondrial uncoupling protein 1 (UCP1) expression and function lead to PVAT/PRAT hypoxia and inflammation as well as vascular, cardiac, and renal dysfunction. As UCP1 function remains an undruggable target so far, modulation of the augmented UCP1-mediated PVAT/PRAT thermogenesis constitutes a lucrative target for drug development to mitigate early cardiorenal involvement. This can be achieved either by subtle targeted reduction in UCP-1 expression using innovative proteolysis activating chimeric molecules (PROTACs) or by supplementation with cyclocreatine phosphate, which augments the mitochondrial futile creatine cycling and thus decreases UCP1 activity, enhances the efficiency of oxygen use, and reduces hypoxia. Once developed, these molecules will be first-in-class therapeutic tools to directly interfere with and reverse the earliest pathology underlying cardiac, vascular, and renal dysfunction accompanying the early metabolic deterioration. SIGNIFICANCE STATEMENT: Adipose tissue dysfunction plays a major role in the pathogenesis of metabolic diseases and their complications. Although mitochondrial alterations are common in metabolic impairment, it was only recently shown that the early stages of metabolic challenge involve inflammatory changes in select adipose depots associated with increased uncoupling protein 1 thermogenesis and hypoxia. Manipulating this mode of thermogenesis can help mitigate the early inflammation and the consequent cardiorenal complications.
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Tejido Adiposo Pardo , Enfermedades Renales , Humanos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/patología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Obesidad/complicaciones , Obesidad/metabolismo , Termogénesis , Inflamación/complicaciones , Inflamación/metabolismo , Hipoxia/metabolismo , Hipoxia/patología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Proteína Desacopladora 1/metabolismoRESUMEN
Entropion is one of the common eyelid marginal malposition and it causes irritation, and ulceration of the cornea that leads to visual loss of a patient. Patient may present with watering and foreign body sensation of the eye initially. Entropion may occur in the upper or lower eyelid. Involutional entropion is common and affected the lower eyelid. There are various non-surgical and surgical options to correct the entropion. Non-surgical procedures include taping the lower eyelid which relieves the entropion temporarily, botulinum toxin type-A injection into lower eyelid may temporarily relief the discomfort from entropion up to 6 months. This study was carried out to assess the outcome of the everting sutures for the correction of lower eyelid involutional entropion and to describe the cost effective of the procedure. A nonrandomized, non control group quasi experimental study was conducted in a Tertiary Eye Hospital, in Gopalganj, Bangladesh from January 2016 to December 2019. A less invasive everting sutures technique was applied for the correction of involutional entropion of eyelid. Follow up was maintained at regular intervals and we assess the outcome of the surgical techniques. We evaluated 33 eyes of 31 patients. The success rate was 87.88%. Recurrences were observed in 5(15.15%) eyelids in the 18 months follow up times. The time of the procedure was only 10 minutes, and the cost of the procedure was cheaper. Everting sutures was minimal invasive, non-incision, cost effective procedure for the correction of involutional entropion.
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Entropión , Humanos , Entropión/cirugía , Análisis Costo-Beneficio , Suturas , Bangladesh , CórneaRESUMEN
In this work, the binding mechanism between donepezil (DNP) and bovine serum albumin (BSA) was established using several techniques, including fluorimetry, UV- spectrophotometry, synchronous fluorimetry (SF), fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET) besides molecular docking study. The fluorescence quenching mechanism of DNP-BSA binding was a combined dynamic and static quenching. The thermodynamic parameters, binding forces, binding constant, and the number of binding sites were determined using a different range of temperature settings. Van't Hoff's equation was used to calculate the reaction parameters, including enthalpy change (ΔHο) and entropy change (ΔSο). The results pointed out that the DNP-BSA binding was endothermic. It was shown that the stability of the drug-protein system was predominantly due to the intermolecular hydrophobic forces. Additionally, the site probing method revealed that subdomain IIA (Site I) is where DNP and BSA's binding occurs. This was validated using a molecular docking study with the most stable DNP configuration. This study might help to understand DNP's pharmacokinetics profile and toxicity as well as provides crucial information for its safe use and avoiding its toxicity.
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In accordance with WHO statistics, leishmaniasis is one of the top neglected tropical diseases, affecting around 700 000 to one million people per year. To that end, a new series of coumarin-1,2,3-triazole hybrid compounds was designed and synthesized. All new compounds exerted higher activity than miltefosine against L. major promastigotes and amastigotes. Seven compounds showed single digit micromolar IC50 values whereas three compounds (13c, 14b and 14c) displayed submicromolar potencies. A mechanistic study to elucidate the antifolate-dependent activity of these compounds revealed that folic and folinic acids abrogated their antileishmanial effects. These compounds exhibited high safety margins in normal VERO cells, expressed as high selectivity indices. Docking simulation studies on the folate pathway enzymes pteridine reductase and DHFR-TS imparted strong theoretical support to the observed biological activities. Besides, docking experiments on human DHFR revealed minimal binding interactions thereby highlighting the selectivity of these compounds. Predicted in silico physicochemical and pharmacokinetic parameters were adequate. In view of this, the structural characteristics of these compounds demonstrated their suitability as antileishmanial lead compounds.
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Antiprotozoarios , Leishmania , Animales , Humanos , Chlorocebus aethiops , Cumarinas/química , Pteridinas/farmacología , Triazoles/farmacología , Triazoles/química , Células VeroRESUMEN
Structural modifications of the antibacterial drug nitrofurantoin were envisioned, employing drug repurposing and biology-oriented drug synthesis, to serve as possible anticancer agents. Eleven compounds showed superior safety in non-cancerous human cells. Their antitumor efficacy was assessed on colorectal, breast, cervical, and liver cancer cells. Three compounds induced oxidative DNA damage in cancer cells with subsequent cellular apoptosis. They also upregulated the expression of Bax while downregulated that of Bcl-2 along with activating caspase 3/7. The DNA damage induced by these compounds, demonstrated by pATM nuclear shuttling, was comparable in both MCF7 and MDA-MB-231 (p53 mutant) cell lines. Mechanistic studies confirmed the dependence of these compounds on p53-mediated pathways as they suppressed the p53-MDM2 interaction. Indeed, exposure of radiosensitive prostatic cancer cells to low non-cytotoxic concentrations of compound 1 enhanced the cytotoxic response to radiation indicating a possible synergistic effect. In vivo antitumor activity was verified in an MCF7-xenograft animal model.
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Antineoplásicos , Neoplasias de la Mama , Animales , Humanos , Femenino , Nitrofurantoína/farmacología , Proteína p53 Supresora de Tumor/genética , Reposicionamiento de Medicamentos , Proliferación Celular , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Biología , Línea Celular TumoralRESUMEN
In 2017, the European Commission installed 24 European Reference Networks (ERNs) for different categories of rare and complex conditions to facilitate cross-border health care via virtual case consultations in a secure Clinical Patient Management System (CPMS). The ERN for rare endocrine conditions (Endo-ERN) previously reviewed the CPMS, in which they detailed the difficulties physicians encountered with the system and proposed solutions to these that should enable the system to be used to a greater extent. This paper will further the endeavor of the first by performing a critical evaluation of the CPMS, assessing how these suggested improvements have been implemented, and if these have affected the usage of the system. The evaluation involves an assessment of CPMS usage statistics since its conception that takes into consideration the technical updates and the external factors that may have affected these, including data from a review survey following a training workshop for our new healthcare providers (HCPs) added in January 2022. It appears that the improvements made to the system since the first review, in particular the implementation of the Operational Helpdesk, have had a positive effect in increasing CPMS membership; however, the regular usage of the system continues to fluctuate. Several suggestions are made on how to further facilitate the use of CPMS by our members both individually and network-wide, by integrating CPMS activities with other network initiatives and further integrating these into national health care systems as well as looking for ways to measure patient satisfaction from the CPMS discussions outcomes.
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An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.
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Hipogonadismo , Enfermedades de la Hipófisis , Pubertad Tardía , Niño , Femenino , Hormonas Esteroides Gonadales/uso terapéutico , Terapia de Reemplazo de Hormonas , Humanos , Hipogonadismo/tratamiento farmacológico , Masculino , Enfermedades de la Hipófisis/tratamiento farmacológico , Pubertad , Pubertad Tardía/tratamiento farmacológico , Testosterona/uso terapéutico , Adulto JovenRESUMEN
Emerging contaminants (ECs) in wastewater have recently attracted the attention of researchers as they pose significant risks to human health and wildlife. This paper presents the state-of-art technologies used to remove ECs from wastewater through a comprehensive review. It also highlights the challenges faced by existing EC removal technologies in wastewater treatment plants and provides future research directions. Many treatment technologies like biological, chemical, and physical approaches have been advanced for removing various ECs. However, currently, no individual technology can effectively remove ECs, whereas hybrid systems have often been found to be more efficient. A hybrid technique of ozonation accompanied by activated carbon was found significantly effective in removing some ECs, particularly pharmaceuticals and pesticides. Despite the lack of extensive research, nanotechnology may be a promising approach as nanomaterial incorporated technologies have shown potential in removing different contaminants from wastewater. Nevertheless, most existing technologies are highly energy and resource-intensive as well as costly to maintain and operate. Besides, most proposed advanced treatment technologies are yet to be evaluated for large-scale practicality. Complemented with techno-economic feasibility studies of the treatment techniques, comprehensive research and development are therefore necessary to achieve a full and effective removal of ECs by wastewater treatment plants.
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Plaguicidas , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Eliminación de Residuos Líquidos , Aguas Residuales/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
We managed to repurpose the old drug iodoquinol to a series of novel anticancer 7-iodo-quinoline-5,8-diones. Twelve compounds were identified as inhibitors of moderate to high potency on an inhouse MCF-7 cell line, of which 2 compounds (5 and 6) were capable of reducing NAD level in MCF-7 cells in concentrations equivalent to half of their IC50s, potentially due to NAD(P)H quinone oxidoreductase (NQO1) inhibition. The same 2 compounds (5 and 6) were capable of reducing p53 expression and increasing reactive oxygen species levels, which further supports the NQO-1 inhibitory activity. Furthermore, 4 compounds (compounds 5-7 and 10) were qualified by the Development Therapeutic Program (DTP) division of the National Cancer Institute (NCI) for full panel five-dose in vitro assay to determine their GI50 on the 60 cell lines. All five compounds showed broad spectrum sub-micromolar to single digit micromolar GI50 against a wide range of cell lines. Cell cycle analysis and dual staining assays with annexin V-FITC/propidium iodide on MCF-7 cells confirmed the capability of the most active compound (compound 5) to induce cell cycle arrest at Pre-G1 and G2/M phases as well as apoptosis. Both cell cycle arrest and apoptosis were affirmed at the molecular level by the ability of compound 5 to enhance the expression levels of caspase-3 and Bax together with suppressing that of CDK1 and Bcl-2. Additionally, an anti-angiogenic effect was evident with compound 5 as supported by the decreased expression of VEGF. Interesting binding modes within NQO-1 active site had been identified and confirmed by both molecular docking and dymanic experiments.
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Antineoplásicos/química , Reposicionamiento de Medicamentos , Yodoquinol/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Sitios de Unión , Puntos de Control del Ciclo Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , NAD/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/antagonistas & inhibidores , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-ActividadRESUMEN
The utilization of renewable lignocellulosic biomasses for bioenergy synthesis is believed to facilitate competitive commercialization and realize affordable clean energy sources in the future. Among the pathways for biomass pretreatment methods that enhance the efficiency of the whole biofuel production process, the combined microwave irradiation and physicochemical approach is found to provide many economic and environmental benefits. Several studies on microwave-based pretreatment technologies for biomass conversion have been conducted in recent years. Although some reviews are available, most did not comprehensively analyze microwave-physicochemical pretreatment techniques for biomass conversion. The study of these techniques is crucial for sustainable biofuel generation. Therefore, the biomass pretreatment process that combines the physicochemical method with microwave-assisted irradiation is reviewed in this paper. The effects of this pretreatment process on lignocellulosic structure and the ratio of achieved components were also discussed in detail. Pretreatment processes for biomass conversion were substantially affected by temperature, irradiation time, initial feedstock components, catalyst loading, and microwave power. Consequently, neoteric technologies utilizing high efficiency-based green and sustainable solutions should receive further focus. In addition, methodologies for quantifying and evaluating effects and relevant trade-offs should be develop to facilitate the take-off of the biofuel industry with clean and sustainable goals.
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Biocombustibles , Microondas , Biomasa , LigninaRESUMEN
The nature of micro- and nanoplastics and their harmful consequences has drawn significant attention in recent years in the context of environmental protection. Therefore, this paper aims to provide an overview of the existing literature related to this evolving subject, focusing on the documented human health and marine environment impacts of micro- and nanoplastics and including a discussion of the economic challenges and strategies to mitigate this waste problem. The study highlights the micro- and nanoplastics distribution across various trophic levels of the food web, and in different organs in infected animals which is possible due to their reduced size and their lightweight, multi-coloured and abundant features. Consequently, micro- and nanoplastics pose significant risks to marine organisms and human health in the form of cytotoxicity, acute reactions, and undesirable immune responses. They affect several sectors including aquaculture, agriculture, fisheries, transportation, industrial sectors, power generation, tourism, and local authorities causing considerable economic losses. This can be minimised by identifying key sources of environmental plastic contamination and educating the public, thus reducing the transfer of micro- and nanoplastics into the environment. Furthermore, the exploitation of the potential of microorganisms, particularly those from marine origins that can degrade plastics, could offer an enhanced and environmentally sound approach to mitigate micro- and nanoplastics pollution.
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Organismos Acuáticos , Contaminantes Químicos del Agua , Animales , Humanos , Microplásticos , Plásticos/toxicidad , Factores Socioeconómicos , Contaminantes Químicos del Agua/análisisRESUMEN
The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC50 values of 0.09-0.14 µM) with significant 15-LOX inhibitory activities (IC50s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates.
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Antiinflamatorios no Esteroideos/farmacología , Antiulcerosos/farmacología , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antiulcerosos/síntesis química , Antiulcerosos/química , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Edema/inducido químicamente , Femenino , Formaldehído , Humanos , Inflamación/inducido químicamente , Macrófagos/efectos de los fármacos , Modelos Moleculares , Pirazoles/síntesis química , Pirazoles/química , Pirazoles/farmacología , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Células THP-1 , Tiazoles/síntesis química , Tiazoles/química , Tiazoles/farmacologíaRESUMEN
Rare endocrine pathology is manifested by either a deficiency or excess of one or more hormones. These conditions can be life-threatening and are almost universally associated with long-term morbidity. Understanding the aetiology of these conditions requires multicentre collaboration and expertise, most often across national boundaries, with the capacity for long-term follow-up. The EuRRECa (European Registries for Rare Endocrine Conditions) project ( www.eurreca.net ), funded by the EU Health Programme, aims to support the needs of the wider endocrine community by maximising the opportunity for collaboration between patients, health care professionals and researchers across Europe and beyond. At the heart of the EuRRECa collaboration is a Core Endocrine Registry that collects a core dataset for all rare endocrine conditions that are covered within Endo-ERN. The registry incorporates patient reported markers of clinical outcome and will signpost participants to high-quality, disease-specific registries. Furthermore, an electronic surveillance programme (e-REC) captures clinical activity and epidemiology for these rare conditions. EuRRECa receives guidance compliant with the highest ethical standards from Expert Working Groups that align with the Main Thematic Groups of Endo-ERN. Security, data quality and data governance are cornerstones of this platform. Clear policies that are acceptable to patients, researchers and industry for data governance coupled with widespread dissemination and knowledge exchange through closely affiliated stakeholders will ensure sustainability beyond the current lifetime of the project. This paper describes the infrastructure that has been developed, stakeholder involvement, the data fields that are captured within the registry and details on the process for using the platform.
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Enfermedades del Sistema Endocrino , Enfermedades Raras , Recolección de Datos , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/terapia , Europa (Continente) , Humanos , Enfermedades Raras/epidemiología , Enfermedades Raras/terapia , Sistema de RegistrosRESUMEN
COVID-19 has heightened human suffering, undermined the economy, turned the lives of billions of people around the globe upside down, and significantly affected the health, economic, environmental and social domains. This study aims to provide a comprehensive analysis of the impact of the COVID-19 outbreak on the ecological domain, the energy sector, society and the economy and investigate the global preventive measures taken to reduce the transmission of COVID-19. This analysis unpacks the key responses to COVID-19, the efficacy of current initiatives, and summarises the lessons learnt as an update on the information available to authorities, business and industry. This review found that a 72-hour delay in the collection and disposal of waste from infected households and quarantine facilities is crucial to controlling the spread of the virus. Broad sector by sector plans for socio-economic growth as well as a robust entrepreneurship-friendly economy is needed for the business to be sustainable at the peak of the pandemic. The socio-economic crisis has reshaped investment in energy and affected the energy sector significantly with most investment activity facing disruption due to mobility restrictions. Delays in energy projects are expected to create uncertainty in the years ahead. This report will benefit governments, leaders, energy firms and customers in addressing a pandemic-like situation in the future.