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OBJECTIVE: Calcium Pyrophosphate Crystal Deposition (CPPD) disease is a chronic and disabling arthropathy. Ultrasound (US) has been shown to be a tool with high sensitivity and specificity for the diagnosis of CPPD disease, but its value at the hip joint has not yet been determined. Therefore, our objective was to evaluate the diagnostic accuracy of US for the identification of calcium pyrophosphate (CPP) crystals in the hip joint as compared with histopathology. METHODS: Diagnostic test study involving patients over 50 years of age with osteoarthritis, scheduled for hip replacement surgery. US was performed on the affected hip. Acetabular fibrocartilage (FC) and hyaline cartilage (HC) of the femoral head were assessed, and a dichotomous score was used for the presence/absence of CPP crystals. Synovial fluid (SF) was obtained from the affected hip and examined using polarized light microscopy. Histopathological examination was performed by an experienced pathologist in search for CPP crystals in FC and HC samples. RESULTS: One hundred patients were enrolled, of whom 62% were found to have hyperechoic areas suggestive of CPP deposition on US examination. Pathological evaluation revealed a prevalence of 61% of CPP crystals. The sensitivity, specificity and the positive predictive and the negative predictive values were 90%, 82%, 89%, and 84%, respectively. The area under the curve for US compared with histopathology for the diagnosis of hip CPPD was 0.86 (CI 95% 0.78-0.94). CONCLUSION: US is a valid imaging modality with good diagnostic accuracy for the detection of hip CPPD.
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OBJECTIVES: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images. METHODS: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics. RESULTS: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75). CONCLUSION: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients.
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Técnica Delphi , Doenças Pulmonares Intersticiais , Ultrassonografia , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Ultrassonografia/normas , Reprodutibilidade dos Testes , Pulmão/diagnóstico por imagem , ConsensoRESUMO
Robotic-assisted orthopedic surgery (RAOS) is revolutionizing the field, offering the potential for increased accuracy and precision and improved patient outcomes. This comprehensive review explores the historical perspective, current robotic systems, advantages and limitations, clinical outcomes, patient satisfaction, future developments, and innovation in RAOS. Based on systematic reviews, meta-analyses, and recent studies, this article highlights the most significant findings and compares RAOS to conventional techniques. As robotic-assisted surgery continues to evolve, clinicians and researchers must stay informed and adapt their practices to provide optimal patient care. Evidence from published studies corroborates these claims, highlighting superior component positioning, decreased incidence of complications, and heightened patient satisfaction. However, challenges such as costs, learning curves, and technical issues must be resolved to fully capitalize on these advantages.
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Procedimentos Ortopédicos , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Previsões , Assistência ao Paciente , Satisfação do PacienteRESUMO
Monoclonal antibodies are among the most effective tools for detecting tumor-associated antigens. The U.S. Food and Drug Administration (FDA) has approved more than 36 therapeutic antibodies for developing novel alternative therapies that have significant success rates in fighting cancer. However, some functional limitations have been described, such as their access to solid tumors and low interaction with the immune system. Single-chain variable fragments (scFv) are versatile and easy to produce, and being an attractive tool for use in immunotherapy models. The small size of scFv can be advantageous for treatment due to its short half-life and other characteristics related to the structural and functional aspects of the antibodies. Therefore, the main objective of this review was to describe the current situation regarding the mechanisms of action, applications, and limitations of monoclonal antibodies and scFv in the treatment of cancer.
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RESUMEN Introducción: El compromiso de la articulación coxofemoral en la artritis reumatoide se asocia a discapacidad y menor calidad de vida. En la actualidad no existen estudios que evalúen sus alteraciones en etapas subclínicas. Objetivos: Determinar la prevalencia del compromiso subclínico de cadera mediante el uso del ultrasonido. Materiales y métodos: Estudio descriptivo de corte transversal, enfocado en pacientes con diagnóstico establecido de artritis reumatoide, según los criterios clasificatorios de la EULAR/ACR 2010, que presentaron o no dolor en la articulación coxofemoral durante el examen físico, comparados con individuos sanos. Se investigó la presencia de distensión de la cápsula articular, bursitis del iliopsoas, erosiones, osteofitos, remodelación articular y serial Doppler de poder. Las imágenes fueron interpretadas por un reumatólogo experto en US, cegado a las variables clínicas, demográficas y de laboratorio. Resultados: Se evaluaron en total 234 caderas; 37 (31,6%) pacientes con artritis reumatoide sintomáticos de la cadera, 40 (34,1%) pacientes con artritis reumatoide subclínica y 40 (34,1%) sujetos sanos. La prevalencia de sinovitis de la cápsula articular fue del 48,6% para los pacien tes con artritis reumatoide sintomática, del 20% para los pacientes con artritis reumatoide subclínica y del 15% para los sujetos sanos. El grupo de pacientes con artritis reumatoide subclínica presentó una mayor frecuencia de osteofitos y remodelación articular. Conclusiones: Se confirmó el valor del ultrasonido en el diagnóstico subclínico de la patología inflamatoria de la articulación coxofemoral. No se evidenciaron asociaciones significativas entre los hallazgos del US con la actividad de la enfermedad, ni con los valores de estudios de laboratorio.
ABSTRACT Introduction: Hip joint involvement in rheumatoid arthritis has been related to disability and lower quality of life. Currently, not enough studies provide information for subclinical hip involvement. Objectives: To determine the prevalence of subclinical hip joint involvement in rheumatoid arthritis, characterizing it by ultrasound. Materials and methods: A descriptive cross-sectional study in rheumatoid arthritis patients with an established diagnosis of rheumatoid arthritis according to EULAR/ACR 2010 classifi cation criteria, without hip pain or abnormalities during a clinical examination (subclinical group), this group was compared with a group of symptomatic patients with rheumatoid arthritis of the hip (pathological control group), and with healthy control individuals mat ched by age and body mass index. The presence of joint capsule distension, osteophytes, joint remodelling process, erosions, iliopsoas bursitis, and power Doppler signal was asses sed. The images were interpreted by an experienced rheumatologist blinded to clinical and laboratory variables. Results: 234 hips were studied; 37 (31.6%) symptomatic hip patients, 40 (34.1%) asymptomatic hip patients and 40 (34.1%) healthy individuals. The prevalence of joint capsule distension was 20%, while symptomatic hip patients and healthy individuals had a prevalence of 48.6% and 15%, respectively. The asymptomatic group presented higher values for osteophytes and joint remodelling. Conclusions: Ultrasound is a sensitive tool to identify subclinical hip joint synovitis in rheumatoid arthritis patients, reaffirming the value of ultrasound in preclinical diagnosis. The presence of erosions and iliopsoas bursitis was low; we observed no power Doppler signals nor significant associations between ultrasound findings with disease activity and laboratory test results.
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Syntenin-1 is a 298 amino acid protein codified by the melanoma differentiation-associated gene-9 (MDA-9). Structurally, it is composed of four domains: N-terminal, PDZ1, PDZ2, and C-terminal. The PDZ domains of syntenin-1 are involved in the stability and interaction with other molecules such as proteins, glycoproteins, and lipids. Domains are also associated with several biological functions such as the activation of signaling pathways related to cell-to-cell adhesion, signaling translation, and the traffic of intracellular lipids, among others. The overexpression of syntenin-1 has been reported in glioblastoma, colorectal, melanoma, lung, prostate, and breast cancer, which promotes tumorigenesis by regulating cell migration, invasion, proliferation, angiogenesis, apoptosis, and immune response evasion, and metastasis. The overexpression of syntenin-1 in samples has been associated with worst prognostic and recurrence, whereas the use of inhibitors such as shRNA, siRNA, and PDZli showed a diminution of the tumor size and reduction in metastasis and invasion. Syntenin-1 has been suggested as a potential biomarker and therapeutic target in cancer for developing more effective diagnostic/prognostic tests or passive/active immunotherapies.
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Benzopyrene is a high-molecular-weight polycyclic aromatic hydrocarbon that is highly recalcitrant and induces carcinogenic effects. CsrA is a conserved regulatory protein that controls the translation and stability of its target transcripts, having negative or positive effects depending on the target mRNAs. It is known that Bacillus licheniformis M2-7 has the ability to grow and survive in certain concentrations of hydrocarbons such as benzopyrene, prompted in part by CsrA, as is present in gasoline. However, there are a few studies that reveal the genes involved in that process. To identify the genes involved in the Bacillus licheniformis M2-7 degradation pathway, the plasmid pCAT-sp containing a mutation in the catE gene was constructed and used to transform B. licheniformis M2-7 and generate a CAT1 strain. We determined the capacity of the mutant B. licheniformis (CAT1) to grow in the presence of glucose or benzopyrene as a carbon source. We observed that the CAT1 strain presented increased growth in the presence of glucose but a statistically considerable decrease in the presence of benzopyrene compared with the wild-type parental strain. Additionally, we demonstrated that the Csr system positively regulates its expression since it was observed that the expression of the gene in the mutant strain LYA12 (M2-7 csrA:: Sp, SpR) was considerably lower than that in the wild-type strain. We were thus able to propose a putative regulation model for catE gene in B. licheniformis M2-7 strain by CsrA regulator in the presence of benzopyrene.
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Bacillus licheniformis , Proteínas Repressoras , Proteínas Repressoras/genética , Bacillus licheniformis/genética , Bacillus licheniformis/metabolismo , Fatores de Transcrição/genética , Mutação , Benzo(a)pireno , Benzopirenos , Regulação Bacteriana da Expressão GênicaRESUMO
To characterize CD4+CD28null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4+CD28null/CD4+ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet+ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt+ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4+ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4+CD28null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4+CD28nullT-bet+ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4+CD28nullGATA-3+ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4+CD28nullRORγt+ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4+CD28null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4+ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.
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Antígenos CD28 , Hiperuricemia , Humanos , Alopurinol/uso terapêutico , Antígenos CD28/metabolismo , Linfócitos T CD4-Positivos , Hiperuricemia/tratamento farmacológico , Leucócitos Mononucleares/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fenótipo , Projetos Piloto , Ácido Úrico/metabolismo , Estudo de Prova de ConceitoRESUMO
Background and Objectives: REST (RE1-silencing transcription factor) diminution is associated with transcriptional relaxation, neuropeptide overexpression, and phenotype redefinition in neuroendocrine cancers, but this effect has barely been studied in cervical cancer (CC). We previously reported reduced expressions of REST in samples with premalignant lesions and CC; however, the transcriptional consequences for neural genes associated with reduced REST expression in CC are unknown. Therefore, the objective of this work was to evaluate the expression of neuronal genes in cancerous cells with reduced expression levels of REST. Materials and Methods: Here, we monitored levels of REST by immunostaining along the premalignant lesions and in invasive cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma (ADC) in tissue samples from female patients from southern Mexico and the derivative cell lines SiHa and HeLa, respectively. Next, we selected REST target genes in silico and explored the effect of REST silencing by RT-PCR in siRNA-treated HeLa cells. Results: The results show a REST diminution in premalignant lesions, SCC, ADC, and cancerous cell lines. Further REST silencing in HeLa cells altered the expression of genes containing the RE1 (Restrictive Element 1) sequence, including CgA (chromogranin A), CHRNß2 (cholinergic receptor nicotinic ß 2 subunit), BDNF (brain-derived neurotrophic factor), CRF (corticotropin-releasing factor), and RASSF1A (Ras association domain family 1). Conclusions: This work provides preliminary evidence of the role of REST loss in the transcriptional regulation of its target genes in HeLa cells, which could have positive implications for the search for new biomarkers of cervical cancer.
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Proteínas Repressoras , Fatores de Transcrição , Neoplasias do Colo do Útero , Feminino , Humanos , Biomarcadores , Expressão Gênica , Células HeLa , RNA Interferente Pequeno , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Proteínas Repressoras/genéticaRESUMO
Fibromyalgia is characterised by widespread musculoskeletal pain, which may present with fatigue, depression, anxiety, sleep and cognitive disturbances. It is the second most prevalent rheumatic disease. An accurate diagnosis is challenging, since its symptoms may resemble diverse conditions such as carpal tunnel syndrome, Raynaud syndrome, Sjögren syndrome, amongst others. Neuropathic pain and autonomic dysfunction in fibromyalgia suggest the involvement of the nervous system. Ion channels, neurotransmitters and neuromodulators may play a role. Small fibre neuropathy (SFN) may also cause chronic widespread pain. SFN may occur in 50% of fibromyalgia patients, but its role in the disease is unknown. Despite several efforts to synthesise the evidence on the mechanisms for pain in fibromyalgia, there are few studies applying an integrative perspective of neurochemical, immunological, and neuroanatomical characteristics, and their relevance to the disease. This protocol aims to clarify the mechanisms of the central and peripheral nervous system associated with pain in fibromyalgia. We will retrieve published studies from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid and Google Scholar. All clinical studies or experimental models of fibromyalgia reporting imaging, neurophysiological, anatomical, structural, neurochemical, or immunological characteristics of the central or peripheral nervous systems associated with pain will be included. Exclusion criteria will eliminate studies evaluating pain without a standardised measure, studies written in languages different from Spanish or English that could not be appropriately translated, and studies whose full-text files could not be retrieved after all efforts made. A narrative synthesis will be performed.
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Dor Crônica , Fibromialgia , Neuralgia , Doenças Reumáticas , Humanos , Fibromialgia/diagnóstico , Dor Crônica/etiologiaRESUMO
OBJECTIVE: To assess the reliability and diagnostic accuracy of new radiographic imaging definitions developed by an international multidisciplinary working group for identification of calcium pyrophosphate deposition (CPPD). METHODS: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and 2 rheumatologists twice assessed radiographic images for presence or absence of CPPD in menisci, hyaline cartilage, tendons, joint capsule, or synovial membrane, using the new definitions. In case of disagreement, a consensus decision was made and considered for the assessment of diagnostic performance. Histologic examination of postsurgical specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa values were used to assess reliability, and diagnostic performance statistics were calculated. RESULTS: Sixty-seven patients were enrolled for the reliability study. The interobserver reliability was substantial in most of the assessed structures when considering all 4 readers (κ range 0.59-0.90), substantial to almost perfect among radiologists (κ range 0.70-0.91), and moderate to almost perfect among rheumatologists (κ range 0.46-0.88). The intraobserver reliability was substantial to almost perfect for all the observers (κ range 0.70-1). Fifty-one patients were included in the accuracy study. Radiography demonstrated an overall specificity of 92% for CPPD, but sensitivity remained low for all sites and for the overall diagnosis (54%). CONCLUSION: The new radiographic definitions of CPPD are highly specific against the gold standard of histologic diagnosis. When the described radiographic findings are present, these definitions allow for a definitive diagnosis of CPPD, rather than other calcium-containing crystal depositions; however, a negative radiographic finding does not exclude the diagnosis.
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Calcinose , Condrocalcinose , Humanos , Pirofosfato de Cálcio , Condrocalcinose/diagnóstico por imagem , Reprodutibilidade dos Testes , Articulação do Joelho/diagnóstico por imagem , RadiografiaRESUMO
OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.
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Antirreumáticos , Artrite Psoriásica , Inibidores de Janus Quinases , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Antirreumáticos/uso terapêutico , Psoríase/tratamento farmacológico , Metotrexato/uso terapêutico , Interleucina-12 , Inibidores de Janus Quinases/uso terapêuticoRESUMO
BACKGROUND: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. METHODS: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. FINDINGS: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). INTERPRETATION: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. FUNDING: The Italian Ministry of Health - Ricerca Corrente.
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Calcinose , Pirofosfato de Cálcio , Humanos , Feminino , Masculino , Reprodutibilidade dos Testes , Difosfatos , UltrassonografiaRESUMO
Abstract The erector spinae plane (ESP) block is an interfascial block described in 2016 by Forero and collaborators, with wide clinical uses and benefits when it comes to analgesic control in different surgeries. This block consists of the application of local anesthetic (LA) in a deep plane over the transverse process, anterior to the erector spinae muscle in the anatomical site where dorsal and ventral branches of the spinal nerve roots are located. This review will cover its clinical uses according to different surgical models, the existing evidence and complications described to date.
Resumen El bloqueo del plano del músculo erector de la espina (ESP, por sus siglas en inglés) es un bloqueo interfascial descrito en 2016 por Forero y colaboradores, con amplios usos clínicos y beneficios en relación con el control analgésico de diferentes modelos quirúrgicos. Este consiste en la aplicación de anestésico local (AL) en un plano profundo sobre apófisis transversa anterior al músculo erector de la espina, sitio anatómico donde se encuentra la bifurcación de los ramos dorsal y ventral de las raíces nerviosas espinales. En esta revisión, se expondrán los usos clínicos según diferentes modelos quirúrgicos, la evidencia que existe de ellos y las complicaciones descritas hasta la actualidad.
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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype due to its greater invasive capacity and non-response to hormone therapy. Several species of the Ficus genus have been used as an alternative to traditional medicine against malignant diseases. Previously, leaf extracts from Ficus crocata (Miq.) Mart. ex Miq. (F. crocata) showed antiproliferative activity in vitro against breast and cervical tumor cells without having a cytotoxic effect on non-tumor cell lines. The purpose of the study was to evaluate the effect of hexane (Hex-EFc), dichloromethane (Dic-EFc), and acetone (Ace-EFc) extracts from F. crocata on the proliferative and invasive capacity of breast cancer cells MCF-7 and MDA-MB-231. Materials and methods: The phytochemical profile was carried out by gas chromatography-mass spectrometry (GC-MS). Cell proliferation, migration, and invasion were determined by MTT, wound closure, and transwell assays, respectively. MMPs activity was analyzed using gelatin zymography, and fluorescence microscopy was used to visualize F-actin distribution. Results: Hex-EFc, Dic-EFc, and Ace-EFc showed cytotoxic activity on MDA-MB-231 tumor cells and, to a lesser extent, on MCF-7 cells, without presenting cytotoxicity at the same concentrations in MCF-10A non-tumor cells. Dic-EFc and Ace-EFc (5-10 µg/mL) reduced the migration capacity of MCF-7 and MDA-MB-231 cells. Interestingly, exposure to Dic-EFc and Ace-EFc (5-10 µg/mL) inhibited the invasive ability of MDA-MB-231 cells, reducing the secretion and activity of MMP-2 and MMP-9, as well as the F-actin distribution. Conclusions: Dic-EFc and Ace-EFc at low concentrations decreased breast cancer cell proliferation and invasiveness, mainly of MDA-MB-231 cells. The above supports the potential use of compounds from leaf extracts of F. crocata in neoadjuvant therapy to reduce the progression of breast cancer tumors, mainly triple-negative tumors.
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Breast cancer is the leading cause of death in women from 20 to 59 years old. The conventional treatment includes surgery, chemotherapy, hormonal therapy, and immunotherapy. This immunotherapy is based on administering monoclonal therapeutic antibodies (passive) or vaccines (active) with therapeutic purposes. Several types of vaccines could be used as potential treatments for cancer, including whole-cell, DNA, RNA, and peptide-based vaccines. Peptides used to develop vaccines are derived from tumor-associated antigens or tumor-specific antigens, such as HER-2, MUC1, ErbB2, CEA, FRα, MAGE A1, A3, and A10, NY-ESO-1, among others. Peptide-based vaccines provide some advantages, such as low cost, purity of the antigen, and the induction of humoral and cellular immune response. In this review, we explore the different types of vaccines against breast cancer with a specific focus on the description of peptide-based vaccines, their composition, immune response induction, and the description of new potential therapeutic targets.
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ABSTRACT Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1β release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1β rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.
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"Paper mills" are unethical outsourcing agencies proficient in fabricating fraudulent manuscripts submitted to scholarly journals. In earlier years, the activity of such companies involved plagiarism, but their processes have gained complexity, involving the fabrication of images and fake results. The objective of this study is to examine the main features of retracted paper mills' articles registered in the Retraction Watch database, from inception to the present, analyzing the number of articles per year, their number of citations, and their authorship network. Eligibility criteria for inclusion: retracted articles in any language due to paper mill activity. Retraction letters, notes, and notices, for exclusion. We collected the associated citations and the journals' impact factors of the retracted papers from Web of Science (Clarivate) and performed a data network analysis using VOSviewer software. This scoping review complies with PRISMA 2020 statement and main extensions. After a thorough analysis of the data, we identified 325 retracted articles due to suspected operations published in 31 journals (with a mean impact factor of 3.1). These retractions have produced 3708 citations. Nearly all retracted papers have come from China. Journal's impact factor lower than 7, life sciences journals, cancer, and molecular biology topics were common among retracted studies. The rapid increase of retractions is highly challenging. Paper mills damage scientific research integrity, exacerbating fraud, plagiarism, fake images, and simulated results. Rheumatologists should be fully aware of this growing phenomenon.
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Pesquisa Biomédica , Má Conduta Científica , Autoria , Humanos , Fator de Impacto de Revistas , Plágio , PublicaçõesRESUMO
Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1ß release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1ß rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.