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BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms. METHODS: A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software. RESULTS: This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and ß1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), ß2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01). CONCLUSION: This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.
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OBJECTIVE: To compare the efficacy of non-invasive brain stimulation (NiBS) such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcutaneous vagus nerve stimulation (taVNS) in upper limb stroke rehabilitation. DATA SOURCES: PubMed, Web of Science, and Cochrane databases were searched from January 2010 to June 2022. DATA SELECTION: Randomized controlled trials (RCTs) assessing the effects of "tDCS", "rTMS", "TBS", or "taVNS" on upper limb motor function and performance in activities of daily livings (ADLs) after stroke. DATA EXTRACTION: Data were extracted by 2 independent reviewers. Risk of bias was evaluated with the Cochrane Risk of Bias tool. DATA SYNTHESIS: 87 RCTs with 3750 participants were included. Pairwise meta-analysis showed that all NiBS except continuous TBS (cTBS) and cathodal tDCS were significantly more efficacious than sham stimulation for motor function (standardized mean difference [SMD] range 0.42-1.20), whereas taVNS, anodal tDCS, and both low and high frequency rTMS were significantly more efficacious than sham stimulation for ADLs (SMD range 0.54-0.99). NMA showed that taVNS was more effective than cTBS (SMD:1.00; 95% CI (0.02-2.02)), cathodal tDCS (SMD:1.07; 95% CI (0.21-1.92)), and Physical rehabilitation alone (SMD:1.46; 95% CI (0.59-2.33)) for improving motor function. P-score found that taVNS is best ranked treatment in improving motor function (SMD: 1.20; 95% CI (0.46-1.95)) and ADLs (SMD:1.20; 95% CI (0.45-1.94)) after stroke. After taVNS, excitatory stimulation protocols (intermittent TBS, anodal tDCS, and HF-rTMS) are most effective in improving motor function and ADLs after acute/sub-acute (SMD range 0.53-1.63) and chronic stroke (SMD range 0.39-1.16). CONCLUSIONS: Evidence suggests that excitatory stimulation protocols are the most promising intervention in improving upper limb motor function and performance in ADLs. taVNS appeared to be a promising intervention for stroke patients, but further large RCTs are required to confirm its relative superiority.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Atividades Cotidianas , Recuperação de Função Fisiológica , Metanálise em Rede , Estimulação Transcraniana por Corrente Contínua/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Magnética Transcraniana/métodos , Extremidade Superior , EncéfaloRESUMO
Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association (P < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.
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Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious issue because they may pose a harmful risk to the environment. The proposal of employing fruit by-products, particularly fruit peels, has gradually attained popularity because scientists found that in many instances peels displayed better biological and pharmacological applications than other sections of the fruit. The aim of this review is to highlight the importance of fruit peel extracts and natural products obtained in food industries along with their other potential biological applications.
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OBJECTIVE: To qualitatively synthesize and quantitatively evaluate the effect of pulmonary rehabilitation (PR) on dyspnea, lung functions, fatigue, exercise capacity, and quality of life (QoL) in patients with COVID-19. DATA SOURCES: PubMed, Web of Science, and Cochrane databases were searched from January 2020 to April 2022. DATA SELECTION: Randomized controlled trials (RCTs) assessing the effect of PR on dyspnea, lung functions, fatigue, exercise capacity, and QoL in patients with COVID-19. DATA EXTRACTION: The mean difference (MD) and a 95% CI were estimated for all the outcome measures using random effect models. The following data were extracted by 2 independent reviewers: (1) first author; (2) publication year; (3) nationality; (4) number of patients included (5) comorbidities; (6) ventilatory support; (7) length of inpatient stay; (8) type of PR; (9) outcome measures; and (10) main findings. The risk of bias was evaluated using the cochrane risk of bias tool. DATA SYNTHESIS: A total of 8 RCTs involving 449 participants were included in the review. PR was found to be significantly effective in improving dyspnea (5 studies, SMD -2.11 [95% CI, -2.96 to -1.27; P<.001]) and exercise capacity (MD 65.85 m [95% CI, 42.86 to 88.83; P<.001]) in patients with both acute and chronic COVID-19 with mild to severe symptoms, whereas fatigue (MD -2.42 [95% CI, -2.72 to -2.11, P<.05]) and lung functions (MD 0.26 L [95% CI, 0.04 to 0.48, P<.05]) were significantly improved in acute COVID-19 patients with mild symptoms. The effect of PR on QoL was inconsistent across studies. PR was found to be safe and feasible for patients with COVID-19. CONCLUSION: Evidence from studies indicates that PR program is superior to no intervention in improving dyspnea, exercise capacity, lung functions, and fatigue in patients with COVID-19. PR appears to be safe and beneficial for both acute and chronic COVID-19 patients.
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COVID-19 , Qualidade de Vida , Dispneia/reabilitação , Tolerância ao Exercício , Fadiga , Humanos , PulmãoRESUMO
This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called "epitome of untouched or underexploited natural resources" and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world.
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Organismos Aquáticos , Produtos Biológicos , Peptídeos , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Aprovação de Drogas , Ecossistema , Humanos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Desenvolvimento Sustentável , Estados Unidos , United States Food and Drug AdministrationRESUMO
OBJECTIVE: We aimed to examine the gender, geographical region and income group of the country of affiliation for editorial leadership (eg, editor-in-chief, section editor, associate editor) and advisors (eg, editorial board members) in top-ranked rehabilitation and sports science journals. METHODS: A list of Scopus indexed, Q1 (25% top) rehabilitation and sports science journals, available under four different journal categories, was prepared based on the data from the Scientific Journal Rankings (SJR) website. The information for editorial leadership and advisors for these journals was obtained and their gender was determined through a multistep process. The country of affiliation of editorial leadership and advisors was used to categorise them to World Bank's different geographical regions and income groups (for countries). RESULTS: There were 7248 editors (35.7% leadership and 64.3% advisors) across 113 rehabilitation and sports science journals. Of all editors, 1792 (24.7%) were women. Women represented 24.5% of editorial leadership positions, 24.8% of advisory roles and 10.4% of editors-in-chief. Editors from South Asia (0.5%) and sub-Saharan Africa (0.6%) had the least representation, while those affiliated with institutions from high-income countries represented 93.5% of leadership roles and 93.1% of advisory positions. Moreover, editors affiliated with institutions from North America occupied almost half of all editorial roles. CONCLUSIONS: Women and researchers affiliated with institutions from low-income and middle-income countries are under-represented on the editorial boards of top-ranked rehabilitation and sports science journals indexed in the Scopus database. Editors are responsible for promoting research in their specific field, and therefore, the current leadership in rehabilitation and sports science journals should consider diversifying their editorial boards by providing equitable opportunities to women and researchers from a broader geographical distribution.
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Medicina , Publicações Periódicas como Assunto , Países em Desenvolvimento , Feminino , Humanos , Renda , LiderançaRESUMO
The recent outbreak of coronavirus disease (COVID-19) has rampaged the world with more than 236 million confirmed cases and over 4.8 million deaths across the world reported by the world health organization (WHO) till Oct 5, 2021. Due to the advent of different variants of coronavirus, there is an urgent need to identify effective drugs and vaccines to combat rapidly spreading virus varieties across the globe. Ferrocene derivatives have attained immense interest as anticancer, antifungal, antibacterial, and antiparasitic drug candidates. However, the ability of ferrocene as anti-COVID-19 is not yet explored. Therefore, in the present work, we have synthesized four new ferrocene Schiff bases (L1-L4) to understand the active sites and biological activity of ferrocene derivatives by employing various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential, and molecular electrostatic potential (MEP). A theoretical insight on synthesized ferrocene Schiff bases was accomplished by molecular docking, frontier molecular orbitals energies, active sites, and molecular descriptors which were further compared with drugs being currently used against COVID-19, i.e., dexamethasone, hydroxychloroquine, favipiravir (FPV), and remdesivir (RDV). Moreover, through the molecular docking approach, we recorded the inhibitions of ferrocene derivatives on core protease (6LU7) protein of SARS-CoV-2 and the effect of substituents on the anti-COVID activity of these synthesized compounds. The computational outcome indicated that L1 has a powerful 6LU7 inhibition of SARS-CoV-2 compared to the currently used drugs. These results could be helpful to design new ferrocene compounds and explore their potential application in the prevention and treatment of SARS-CoV-2.
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OBJECTIVE: This review analyzed the current evidence and the potential for the application of electric neurostimulation such as transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS) in upper limb stroke rehabilitation. MATERIALS AND METHODS: We performed a systematic review of randomized controlled trials (RCTs) using network meta-analysis (NMA), searching the following data bases: PubMed, Web of Science, Cochrane, and Google Scholar, using specific keywords, from January 2010 to April 2021, and assessing the effects of "tDCS" or "VNS" combined with other therapies on upper limb motor function and activities of daily living (ADL) after stroke. RESULTS: We included 38 RCTs with 1261 participants. Pairwise NMA showed transcutaneous VNS (tVNS) and anodal tDCS were effective in improving upper limb motor function (tVNS: mean difference [MD]: 5.50; 95% CI [0.67-11.67]; p < 0.05; anodal tDCS: MD: 5.23; 95% CI [2.45-8.01]; p < 0.05). tVNS and tDCS (anodal and cathodal) were also effective in improving ADL performance after stroke (tVNS: standard MD [SMD]: 0.96; 95% CI [0.15-2.06]; p < 0.05; anodal tDCS: SMD: 3.78; 95% CI [0.0-7.56]; p < 0.05; cathodal tDCS: SMD: 5.38; 95% CI [0.22-10.54]; p < 0.05). Surface under the cumulative ranking curve analysis revealed that tVNS is the best ranked treatment in improving upper limb motor function and performance in ADL after stroke. There was no difference in safety between VNS and its control interventions, measured by reported adverse events (VNS: risk ratio = 1.02 [95% CI = 0.48-2.17; I2 = 0; p = 0.96]). CONCLUSION: Moderate- to high-quality evidence suggests that tVNS and anodal tDCS were effective in improving upper limb motor function in both acute/subacute and chronic stroke. In addition to tVNS and anodal tDCS, cathodal tDCS is also effective in improving ADL performance after stroke.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Metanálise em Rede , Recuperação de Função Fisiológica , Ensaios Clínicos Controlados Aleatórios como Assunto , Extremidade Superior , Acidente Vascular Cerebral/terapiaRESUMO
Benzimidazole ring system is an important pharmacophore with diverse pharmacological activities. In this study, we explored the anti-arthritic effects of newly synthesized acetamide derivatives of 2-aminobenzimidazole (N1 and N2) in rats. FTIR and NMR spectroscopies were used to characterize these compounds. Carrageenan (CRG) induced paw edema model was used to test the acute anti-inflammatory activity of various doses (10, 20 and 30 mg/kg) of N1 and N2 compounds. Based on acute anti-inflammatory effects, the most potent dose of each compound was selected and investigated in complete freund's adjuvant (CFA) induced inflammatory arthritis (RA) model (n = 4 in each group). Histopathological, hematological, radiographic, and RT-qPCR analyses were performed to assess the progression or resolution of inflammatory arthritis. The tested compounds produced a dose-dependent anti-inflammatory activity against CRG induced paw inflammation and similarly reduced edema in CFA induced inflammatory arthritis model. Histopathological and X-ray analyses of ankle joints revealed minimal inflammation and normal joint structures in N1 and N2 treated groups. The tested compounds also reduced the levels of autoantibodies and restored hematological parameters. Interestingly, the tested compounds did not elevate aspartate aminotransferase and alanine transaminase levels and displayed a better safety profile than methotrexate. N1 and N2 compounds also attenuated the transcript levels of IRAK1, NF-kB1, TNF-α, IL-1ß, IL17 and MMP1. In addition, N1 displayed a greater inhibition of mRNA levels of COX1, COX2, mPGES1 and PTGDS as compared to N2. Our findings demonstrate that N1 and N2 compounds possess strong anti-arthritic activity which can be attributed to the suppression of pro-inflammatory mediators.
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Artrite Experimental , Mediadores da Inflamação , Acetamidas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/patologia , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Carragenina/farmacologia , Citocinas , Edema/tratamento farmacológico , Adjuvante de Freund , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , RatosRESUMO
In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.
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Doenças Autoimunes do Sistema Nervoso/metabolismo , Endocanabinoides/metabolismo , Receptores de Canabinoides/metabolismo , Animais , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Citocinas/metabolismo , Endocanabinoides/farmacologia , Endocanabinoides/uso terapêutico , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Leucócitos/metabolismo , Receptores de Canabinoides/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Reliability and validity are among the most important and fundamental domains in the assessment of any measuring methodology for data-collection in a good research. Validity is about what an instrument measures and how well it does so, whereas reliability concerns the truthfulness in the data obtained and the degree to which any measuring tool controls random error. The current narrative review was planned to discuss the importance of reliability and validity of data-collection or measurement techniques used in research. It describes and explores comprehensively the reliability and validity of research instruments and also discusses different forms of reliability and validity with concise examples. An attempt has been taken to give a brief literature review regarding the significance of reliability and validity in medical sciences.
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Pesquisa Biomédica , Humanos , Reprodutibilidade dos TestesRESUMO
The objective of this study was to determine the diagnostic accuracy of B-scan in predicting retinoblastoma (Rb) taking Magnetic Resonance Imaging (MRI) as a gold standard. A cross-sectional validation study was conducted in the Radiology Department of Fauji Foundation Hospital from May 20 to Nov 20, 2017. Children fulfilling the inclusion criteria were selected after informed consent and detailed history was taken for investigation of Rb. B-scan of both eyes was done using 7.5-10 MHz probe, followed by MRI of both eyes in the same patients using 1.5 Tesla MRI machine with the help of qualified MRI technicians. Data analysis was done by SPSS version 16.0. The diagnostic accuracy, sensitivity, specificity, PPV and NPV of B-scan in prediction of Rb as compared to MRI was 90.45%, 82.28%, 90.54% and 90.28% respectively. The study concluded that diagnostic accuracy of B-scan as compared to MRI is substantial in Retinoblastoma.
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Neoplasias da Retina , Retinoblastoma , Criança , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética , Órbita , Neoplasias da Retina/diagnóstico por imagem , Retinoblastoma/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
Activating mutations in FLT3 receptor tyrosine kinase are found in a third of acute myeloid leukemia (AML) patients and are associated with disease relapse and a poor prognosis. The majority of these mutations are internal tandem duplications (ITDs) in the juxtamembrane domain of FLT3, which have been validated as a therapeutic target. The clinical success of selective inhibitors targeting oncogenic FLT3, however, has been limited due to the acquisition of drug resistance. Herein the identification of a dual FLT3/microtubule polymerization inhibitor, chalcone 4 (2'-allyloxy-4,4'-dimethoxychalcone), is reported through screening of 15 related chalcones for differential antiproliferative activity in leukemia cell lines dependent on FLT3-ITD (MV-4-11) or BCR-ABL (K562) oncogenes and by subsequent screening for mitotic inducers in the HCT116 cell line. Three natural chalcones (1-3) were found to be differentially more potent toward the MV-4-11 (FLT3-ITD) cell line compared to the K562 (BCR-ABL) cell line. Notably, the new semisynthetic chalcone 4, which is a 2'-O-allyl analogue of the natural chalcone 3, was found to be more potent toward the FLT3-ITD+ cell line and inhibited FLT3 signaling in FLT3-dependent cells. An in vitro kinase assay confirmed that chalcone 4 directly inhibited FLT3. Moreover, chalcone 4 induced mitotic arrest in these cells and inhibited tubulin polymerization in both cellular and biochemical assays. Treatment of MV-4-11 cells with this inhibitor for 24 and 48 h resulted in apoptotic cell death. Finally, chalcone 4 was able to overcome TKD mutation-mediated acquired resistance to FLT3 inhibitors in a MOLM-13 cell line expressing FLT3-ITD with the D835Y mutation. Chalcone 4 is, therefore, a promising lead for the discovery of dual-target FLT3 inhibitors.
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Antibióticos Antineoplásicos/farmacologia , Chalconas/farmacologia , Microtúbulos/metabolismo , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Chalconas/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores Enzimáticos/farmacologia , Células HCT116 , Humanos , Células K562 , Leucemia Mieloide Aguda/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Polimerização , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the skin in cats. Tumour angiogenesis is the pivotal event for tumour progression and metastasis. We assessed protein and gene expression of angiogenic growth factors including bFGF, VEGF-C, TGF-ß, PDGF-A, PDGF-C and PDGFR-α that possibly contribute to the angiogenic phenotype of feline SCC (FSCC) and could, therefore, be a good target in the treatment of SCC. In the present study, a total of 27 FSCC cases were investigated. Tumour cases were histopathologically classified as well differentiated (10/27), moderately differentiated (5/27), and poorly differentiated (12/27). The expression levels of the growth factors were detected using immunohistochemistry and assessed semi-quantitatively. Growth factor expression levels were evaluated at different locations: in the oral region, in areas exposed to solar UV radiation including the ears, eyelids and nasal planum, and other miscellaneous locations. Our findings have revealed that FSCC arising from different anatomical sites of the body and showing differences in aggressiveness, metastasis, and prognosis may be angiogenesis dependent, and angiogenic key regulators could play a role in the development of FSCC.
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Carcinoma de Células Escamosas/veterinária , Doenças do Gato/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neovascularização Patológica , Neoplasias Cutâneas/veterinária , Animais , Carcinoma de Células Escamosas/genética , Gatos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Cutâneas/genéticaRESUMO
Staining compounds containing heavy elements (electron dyes) can facilitate the visualization of DNA and related biomolecules by using TEM. However, research into the synthesis and utilization of alternative electron dyes has been limited. Here, we report the synthesis of a novel DNA intercalator molecule, bis-acridine uranyl (BAU). NMR spectroscopy and MS confirmed the validity of the synthetic strategy and gel electrophoresis verified the binding of BAU to DNA. For TEM imaging of DNA, two-dimensional DNA origami nanostructures were used as a robust microscopy test object. By using scanning transmission electron microscopy (STEM) imaging, which is favored over conventional wide-field TEM for improved contrast, and therefore, quantitative image analysis, it is found that the synthesized BAU intercalator can render DNA visible, even at the single-molecule scale. For comparison, other staining compounds with a purported affinity towards DNA, such as dichloroplatinum, cisplatin, osmium tetroxide, and uranyl acetate, have been evaluated. The STEM contrast is discussed in terms of the DNA-dye association constants, number of dye molecules bound per base pair, and the electron-scattering capacity of the metal-containing ligands. These findings pave the way for the future development of electron dyes with specific DNA-binding motifs for high-resolution TEM imaging.
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Acridinas/química , Complexos de Coordenação/química , DNA/química , Substâncias Intercalantes/química , Imagem Individual de Molécula/métodos , Acridinas/síntese química , Complexos de Coordenação/síntese química , Substâncias Intercalantes/síntese química , Microscopia Eletrônica de Transmissão e Varredura/métodos , Conformação de Ácido Nucleico , Urânio/químicaRESUMO
In recent years, the demand for naturally derived products has hiked with enormous pressure to propose or develop state-of-the-art strategies to meet sustainable circular economy challenges. Microalgae possess the flexibility to produce a variety of high-value products of industrial interests. From pigments such as phycobilins or lutein to phycotoxins and several polyunsaturated fatty acids (PUFAs), microalgae have the potential to become the primary producers for the pharmaceutical, food, and agronomical industries. Also, microalgae require minimal resources to grow due to their autotrophic nature or by consuming waste matter, while allowing for the extraction of several valuable side products such as hydrogen gas and biodiesel in a single process, following a biorefinery agenda. From a Mexican microalgae biodiversity perspective, more than 70 different local species have been characterized and isolated, whereas, only a minimal amount has been explored to produce commercially valuable products, thus ignoring their potential as a locally available resource. In this paper, we discuss the microalgae diversity present in Mexico with their current applications and potential, while expanding on their future applications in bioengineering along with other industrial sectors. In conclusion, the use of available microalgae to produce biochemically revenuable products currently represents an untapped potential that could lead to the solution of several problems through green technologies. As such, if the social, industrial and research communities collaborate to strive towards a greener economy by preserving the existing biodiversity and optimizing the use of the currently available resources, the enrichment of our society and the solution to several environmental problems could be attained.
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Biodiversidade , Bioengenharia/métodos , Produtos Biológicos/química , Microalgas/química , Crescimento Sustentável , Biocombustíveis , Biomassa , MéxicoRESUMO
A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a-n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c-e, 6g, and 6i were found to be promising inhibitors of α-glucosidase with IC50 values of 81.72 ± 1.18, 52.73 ± 1.16, 62.62 ± 1.15, 56.34 ± 1.17, 86.35 ± 1.17, 52.63 ± 1.16 µM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.