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Aggressive angiomyxoma (AAM) is a rare benign tumor that arises from connective tissue, prominently located in the vulva, vagina, perineum, and pelvis and is mainly found in women aged about 20-40 years old. Giant intraabdominal tumors have rarely been described. These tumors develop slowly over time and are often difficult to diagnose due to various clinical findings, especially in the early stages. Even though surgery is the primary treatment method, the possibility of complete resection is sometimes limited because the tumor tends to infiltrate nearby structures, leading to local recurrence. Only about 10% of AAM cases can be accurately diagnosed before treatment, which causes ineffective outcomes. This article demonstrates a case of giant intra-abdominal AAM precisely diagnosed by suspicious signs on CT and MRI scans before starting treatment.
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Triple-negative breast cancer (TNBC) cells are often resistant to FAS (CD95)-mediated apoptosis, but the underlying molecular mechanism(s) is not fully understood yet. Notably, the expression of the type II transmembrane protein, CD74, is correlated with chemotherapy-resistant and more invasive forms of cancers via unknown mechanisms. Here, we analyzed gene expression pattern of cancer patients and/or patient-derived xenograft (PDX) models and found that mRNA and protein levels of CD74 are highly expressed in TNBC and correlated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) properties. Mechanistically, we found that AKT activation is likely critical for maintaining CD74 expression and protein stability to favor its oncogenic functions. Physiologically, epidermal growth factor (EGF) along with CD74 could activate AKT signaling, likely through binding of phosphorylated AKT (S473) to CD74, whereas inhibition of AKT could impair stability of CD74. We also revealed that CD74 binds to FAS and interferes with the intrinsic signaling of FAS-mediated apoptosis. As such, selective targeting of the CD74/FAS complex using the AKT inhibitor along with the CD74-derived peptide could synergistically restore and activate FAS-mediated apoptosis. Therefore, our approach of mobilizing apoptosis pathways likely provides a rationale for TNBC treatment by targeting the CD74/FAS and CD74-AKT axes.
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The disialoganglioside, GD2, is a promising therapeutic target due to its overexpression in certain tumors, particularly neuroblastoma (NB), with limited expression in normal tissues. Despite progress, the intricate mechanisms of action and the full spectrum of the direct cellular responses to anti-GD2 antibodies remain incompletely understood. In this study, we examined the direct cytotoxic effects of the humanized anti-GD2 antibody hu14.18K322A (hu14) on NB cell lines, by exploring the associated cell-death pathways. Additionally, we assessed the synergy between hu14 and conventional induction chemotherapy drugs. Our results revealed that hu14 treatment induced direct cytotoxic effects in CHLA15 and SK-N-BE1 cell lines, with a pronounced impact on proliferation and colony formation. Apoptosis emerged as the predominant cell-death pathway triggered by hu14. Furthermore, we saw a reduction in GD2 surface expression in response to hu14 treatment. Hu14 demonstrated synergy with induction chemotherapy drugs with alterations in GD2 expression. Our comprehensive investigation provides valuable insights into the multifaceted effects of hu14 on NB cells, shedding light on its direct cytotoxicity, cell-death pathways, and interactions with induction chemotherapy drugs. This study contributes to the evolving understanding of anti-GD2 antibody therapy and its potential synergies with conventional treatments in the context of NB.
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N-Pyridinylthiophene carboxamide (compound 21) displays activity against peripheral nerve sheath cancer cells and mouse xenografts by an unknown mechanism. Through medicinal chemistry, we identified a more active derivative, compound 9, and found that only analogues with structures similar to nicotinamide retained activity. Genetic screens using compound 9 found that both NAMPT and NMNAT1, enzymes in the NAD salvage pathway, are necessary for activity. Compound 9 is metabolized by NAMPT and NMNAT1 into an adenine dinucleotide (AD) derivative in a cell-free system, cultured cells, and mice, and inhibition of this metabolism blocked compound activity. AD analogues derived from compound 9 inhibit IMPDH in vitro and cause cell death by inhibiting IMPDH in cells. These findings nominate these compounds as preclinical candidates for the development of tumor-activated IMPDH inhibitors to treat neuronal cancers.
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NAD , Niacinamida , Tiofenos , Animais , NAD/metabolismo , Humanos , Camundongos , Niacinamida/análogos & derivados , Niacinamida/metabolismo , Niacinamida/farmacologia , Niacinamida/química , Tiofenos/farmacologia , Tiofenos/química , Tiofenos/metabolismo , Linhagem Celular Tumoral , IMP Desidrogenase/antagonistas & inibidores , IMP Desidrogenase/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Nicotinamida Fosforribosiltransferase/metabolismo , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Neoplasias de Bainha Neural/tratamento farmacológico , Neoplasias de Bainha Neural/metabolismo , Neoplasias de Bainha Neural/patologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo , Nicotinamida-Nucleotídeo Adenililtransferase/antagonistas & inibidoresRESUMO
This research aimed to explore factors associated with the fear of falling (FOF) among community-dwelling older adults in Vietnam. A cross-sectional study was conducted in five communes in Soc Son, Hanoi, Vietnam, from March to June 2017. We recruited a total of 487 participants, which provided sufficient data for analysis. The outcome variable was fear of falling. Several covariates, including demographics, medical history, general health status, geriatric syndromes, eye diseases, assessment of fall risk environment, timed up-and-go test, and number of standing up in 30 s, were collected. A multivariable logistic regression model was performed to determine predictors associated with FOF. The results showed that 54.6% of the participants had FOF. Furthermore, the logistic multivariable regression model revealed several factors associated with FOF among participants in the research sites, including polypharmacy status (OR: 1.79; 95%CI 1.07-2.99), higher scores in quality of life according to the EQ-5D-5L index (OR:6.27; 95%CI: 2.77-14.17), and having fallen during the past 12 months (OR:4.4; 95%CI: 2.39-8.11). These findings contribute to a comprehensive understanding of the intricate relationship between FOF and several associated factors, notably polypharmacy status, quality of life, and having a fall during the past 12 months.
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Acidentes por Quedas , Medo , População Rural , Humanos , Acidentes por Quedas/estatística & dados numéricos , Idoso , Vietnã , Masculino , Feminino , Medo/psicologia , Estudos Transversais , População Rural/estatística & dados numéricos , Idoso de 80 Anos ou mais , Vida Independente/psicologia , Qualidade de Vida , Fatores de Risco , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIM: The efficacy of melatonin and its biological significance in human bladder cancer remain poorly understood. This study aimed to investigate the functional role of melatonin in urothelial carcinogenesis. MATERIALS AND METHODS: In human normal urothelial SVHUC cells with exposure to the chemical carcinogen 3-methylcholanthrene, we assessed the effects of melatonin on the neoplastic/malignant transformation. RESULTS: In the in vitro system with carcinogen challenge, melatonin significantly prevented the neoplastic transformation of SV-HUC-1 cells. In addition, melatonin treatment resulted in increased expression of SIRT1, Rb1, and E-cadherin, and decreased expression of N-cadherin and FGFR3 in SV-HUC-1 cells. Furthermore, publicly available datasets from GSE3167 revealed that the expression of melatonin receptor 1 and melatonin receptor 2 was significantly down-regulated in bladder urothelial carcinoma tissues, compared with adjacent normal urothelial tissues. CONCLUSION: These findings indicate that melatonin serves as a suppressor for urothelial tumorigenesis. To the best of our knowledge, this is the first preclinical study demonstrating the impact of melatonin on the development of urothelial cancer.
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Carcinógenos , Transformação Celular Neoplásica , Melatonina , Neoplasias da Bexiga Urinária , Urotélio , Melatonina/farmacologia , Humanos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Carcinógenos/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/patologia , Urotélio/metabolismo , Urotélio/efeitos dos fármacos , Metilcolantreno/toxicidadeRESUMO
Highly colored azo dye-contaminated wastewater poses significant environmental threats and requires effective treatment before discharge. The anaerobic azo dye treatment method is a cost-effective and environmentally friendly solution, while its time-consuming and inefficient processes present substantial challenges for industrial scaling. Thus, the use of iron materials presents a promising alternative. Laboratory studies have demonstrated that systems coupled with iron materials enhance the decolorization efficiency and reduce the processing time. To fully realize the potential of iron materials for anaerobic azo dye treatment, a comprehensive synthesis and evaluation based on individual-related research studies, which have not been conducted to date, are necessary. This review provides, for the first time, an extensive and detailed overview of the utilization of iron materials for azo dye treatment, with a focus on decolorization. It assesses the treatment potential, analyzes the influencing factors and their impacts, and proposes metabolic pathways to enhance anaerobic dye treatment using iron materials. The physicochemical characteristics of iron materials are also discussed to elucidate the mechanisms behind the enhanced bioreduction of azo dyes. This study further addresses the current obstacles and outlines future prospects for industrial-scale application of iron-coupled treatment systems.
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Compostos Azo , Corantes , Ferro , Águas Residuárias , Poluentes Químicos da Água , Compostos Azo/química , Corantes/química , Águas Residuárias/química , Poluentes Químicos da Água/química , Ferro/química , Eliminação de Resíduos Líquidos/métodos , Descoloração da Água/métodosRESUMO
Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.
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Antineoplásicos , Neoplasias da Mama , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Compostos Organofosforados , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Compostos Organofosforados/síntese química , Relação Estrutura-Atividade , Células MCF-7 , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/antagonistas & inibidores , Feminino , Descoberta de Drogas , Estrutura Molecular , Relação Dose-Resposta a Droga , FlavanonasRESUMO
We recently discovered a novel N-aryl tetracyclic dicarboximide MM0299 (1) with robust activity against glioma stem-like cells that potently and selectively inhibits lanosterol synthase leading to the accumulation of the toxic shunt metabolite 24(S),25-epoxycholesterol. Herein, we delineate a systematic and comprehensive SAR study that explores the structural space surrounding the N-aryl tetracyclic dicarboximide scaffold. A series of 100 analogs were synthesized and evaluated for activity against the murine glioma stem-like cell line Mut6 and for metabolic stability in mouse liver S9 fractions. This study led to several analogs with single-digit nanomolar activity in Mut6 glioblastoma cells that were metabolically stable in S9 fractions. In vivo pharmacokinetic analysis of selected analogs identified compound 52a (IC50 = 63 nM; S9 T1/2 > 240 min) which was orally available (39% plasma; 58% brain) and displayed excellent brain exposure. Chronic oral dosing of 52a during a 2-week tolerability study indicated no adverse effect on body weight nor signs of hematologic, liver, or kidney toxicity.
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Glioma , Células-Tronco Neoplásicas , Animais , Camundongos , Relação Estrutura-Atividade , Glioma/tratamento farmacológico , Glioma/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Descoberta de Drogas , Masculino , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologiaRESUMO
BACKGROUND: The use of ointments can be beneficial for dry, chapped, or cracked skin and also for supporting wound healing. We describe the results of 2 studies with an over-the-counter healing ointment (HO) to evaluate the effects on skin hydration and in the setting of wound healing after dermatologic procedures. Methods: Study 1 was a single-center, in-use study using HO on qualified areas at least once daily for 4 weeks in subjects with dry, cracked body skin and self-perceived sensitive skin. Study 2 was a multi-center study of wound healing in subjects using HO on a daily basis after having dermatologic surgical procedures. Results: In Study 1, there was a significant reduction in skin dryness after 1 and 4 weeks of HO use (P<0.05). Image analysis of the skin revealed a significant increase in skin smoothness after the first application of HO in 100% of subjects (P<0.05). Tolerability and safety were excellent, and HO was well-perceived by subjects throughout the study. In Study 2, HO improved clinical assessments at all time points compared with baseline with a decrease in erythema, edema, scabbing/crusting, and an improvement in overall wound appearance (P<0.05). There was no worsening or significant increase in measures for tolerability parameters at any study visits. Additionally, HO achieved a favorable perception by study subjects. Conclusions: HO has a well-established safety profile and has been shown to improve both skin hydration and the overall wound healing process after dermatologic surgical procedures. J Drugs Dermatol. 2024;23(5):360-365. doi:10.36849/JDD.8224.
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Medicamentos sem Prescrição , Pomadas , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Medicamentos sem Prescrição/administração & dosagem , Idoso , Resultado do Tratamento , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Pele/patologia , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Adulto Jovem , Administração CutâneaRESUMO
BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.
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Antagonistas de Androgênios , Neoplasias da Próstata , Testosterona , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/sangue , Testosterona/sangue , Testosterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fatores de TempoRESUMO
OBJECTIVES: With targeted therapies, people are surviving longer with advanced lung cancer and engaging in online lung cancer support communities. While these groups provide a sense of community, witnessing the death of peers can lead to emotional distress. This qualitative study aims to (1) explore the experience of witnessing death in online cancer support groups; (2) identify factors that contribute to the emotional struggles of witnessing the death of peers; and (3) identify strategies/options for dealing with losses in the cancer community. METHODS: We conducted a cross-sectional analysis of qualitative interviews exploring existential concerns with participants (n = 25) from oncogene-specific online lung cancer support groups. The principal investigator conducted study interviews between August 2018 and March 2019 where participants were asked about their cancer experiences and existential concerns. We used thematic analysis and NVIVO 11 software to examine and store the de-identified interview data. RESULTS: Participants indicated that they had often witnessed their peers die and felt the pain of the loss. Factors that played a part in their struggle with witnessing others' death included the closeness of the relationship with the person, the age of the person who died, seeing oneself in the experience of the other dying, disparities in care, and losing touch in the final stages. Participants used varied coping strategies such as celebrating the life of the individual who died, engaging in advocacy efforts, not focusing on the loss, participating in therapy, and bringing self-preserving thoughts. SIGNIFICANCE OF RESULTS: Our study highlights the importance of addressing existential fears in online lung cancer support groups and incorporating conversations about death in spaces that deal with cancer.
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Purpose: Cultured lichen mycobionts are valuable sources of new natural compounds. Mycobiont of Graphis handelii growing in Vietnam was isolated, cultivated and chemically investigated. The crude extract of this cultured mycobiont showed potent alpha-glucosidase inhibition with an IC50 value of 50 µg/mL. Methods: Multiple chromatographic methods were applied to the extract to isolate compounds. The combination of Nuclear Magnetic Resonance analysis and high-resolution mass spectroscopy determined their chemical structures. Electrophilic bromination/chlorination was applied to obtain new derivatives using NaBr/H2O2 and NaCl/H2O2 reagents. Compounds were evaluated for enzyme inhibitory activities, including alpha-glucosidase inhibition, HIV-1 reverse transcriptase inhibition, SARS-CoV-2 main protease (Mpro) inhibition, anti-inflammatory activity, and cytotoxicity against several cancer cell lines. A molecular docking study for anti-SARS-CoV-2 was conducted to understand the inhibitory mechanism. Results: A new diphenyl ether, handelone (1) and a known compound xylarinic acid A (2) were isolated and elucidated. Four synthetic products 6'-bromohandelone (1a), 2'-bromohandelone (1b), 2',6'-dibromohandelone (1c), and 2',6'-dichlorohandelone (1d) were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays. Conclusion: A new compound, handelone (1) was isolated from the cultured mycobiont of Graphis handelii. From these compounds, four new derivatives were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.
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Cordyceps militaris is a well-known medicinal mushroom in Asian countries. This edible fungus has been widely exploited for traditional medicine and functional food production. C. militaris is a heterothallic fungus that requires both the mating-type loci, MAT1-1 and MAT1-2, for fruiting body formation. However, recent studies also indicated two groups of C. militaris, including monokaryotic strains carrying only MAT1-1 in their genomes and heterokaryotic strains harboring both MAT1-1 and MAT1-2. These strain groups are able to produce fruiting bodies under suitable cultivating conditions. In previous work, we showed that monokaryotic strains are more stable than heterokaryotic strains in fruiting body formation through successive culturing generations. In this study, we report a high cordycepin-producing monokaryotic C. militaris strain (HL8) collected in Vietnam. This strain could form normal fruiting bodies with high biological efficiency and contain a cordycepin content of 14.43 mg/g lyophilized fruiting body biomass. The ethanol extraction of the HL8 fruiting bodies resulted in a crude extract with a cordycepin content of 69.15 mg/g. Assays of cytotoxic activity on six human cancer cell lines showed that the extract inhibited the growth of all these cell lines with the IC50 values of 6.41-11.51 µg/mL. Notably, the extract significantly reduced cell proliferation and promoted apoptosis of breast cancer cells. Furthermore, the extract also exhibited strong antifungal activity against Malassezia skin yeasts and the citrus postharvest pathogen Penicillium digitatum. Our work provides a promising monokaryotic C. militaris strain as a bioresource for medicine, cosmetics, and fruit preservation.
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Antineoplásicos , Cordyceps , Neoplasias , Penicillium , Humanos , Penicillium/genética , CarpóforosRESUMO
The NLRP3 inflammasome is a cytosolic protein complex important for the regulation and secretion of inflammatory cytokines, including IL-1ß and IL-18. Aberrant overactivation of NLRP3 is implicated in numerous inflammatory disorders. However, the activation and regulation of NLRP3 inflammasome signaling remain poorly understood, limiting our ability to develop pharmacologic approaches to target this important inflammatory complex. Here, we developed and implemented a high-throughput screen to identify compounds that inhibit the inflammasome assembly and activity. From this screen, we identify and profile inflammasome inhibition of 20 new covalent compounds across nine different chemical scaffolds, as well as many known inflammasome covalent inhibitors. Intriguingly, our results indicate that NLRP3 possesses numerous reactive cysteines on multiple domains whose covalent targeting blocks the activation of this inflammatory complex. Specifically, focusing on compound VLX1570, which possesses multiple electrophilic moieties, we demonstrate that this compound allows covalent, intermolecular cross-linking of NLRP3 cysteines to inhibit inflammasome assembly. Our results, along with the recent identification of numerous covalent molecules that inhibit NLRP3 inflammasome activation, further support the continued development of electrophilic compounds that target reactive cysteine residues on NLRP3 to regulate its activation and activity.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Citocinas , Interleucina-1beta/metabolismoRESUMO
The surface-enhanced Raman scattering (SERS) technique has garnered significant interest due to its ultrahigh sensitivity, making it suitable for addressing the growing demand for disease diagnosis. In addition to its sensitivity and uniformity, an ideal SERS platform should possess characteristics such as simplicity in manufacturing and low analyte consumption, enabling practical applications in complex diagnoses including cancer. Furthermore, the integration of machine learning algorithms with SERS can enhance the practical usability of sensing devices by effectively classifying the subtle vibrational fingerprints produced by molecules such as those found in human blood. In this study, we demonstrate an approach for early detection of breast cancer using a bottom-up strategy to construct a flexible and simple three-dimensional (3D) plasmonic cluster SERS platform integrated with a deep learning algorithm. With these advantages of the 3D plasmonic cluster, we demonstrate that the 3D plasmonic cluster (3D-PC) exhibits a significantly enhanced Raman intensity through detection limit down to 10-6 M (femtomole-(10-17 mol)) for p-nitrophenol (PNP) molecules. Afterward, the plasma of cancer subjects and healthy subjects was used to fabricate the bioink to build 3D-PC structures. The collected SERS successfully classified into two clusters of cancer subjects and healthy subjects with high accuracy of up to 93%. These results highlight the potential of the 3D plasmonic cluster SERS platform for early breast cancer detection and open promising avenues for future research in this field.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Análise Espectral Raman/métodosRESUMO
BACKGROUND: There remains limited knowledge about the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in pediatric oncology patients, which is essential to provide counseling and risk adaptation in this vulnerable population. The goal of this study was to understand immunogenicity after vaccination in pediatric oncology patients, and determine if certain clinical factors impacted response. METHODS: Patients 0-25 years of age with a diagnosis of cancer and actively receiving therapy were enrolled on study. We excluded patients who were completely vaccinated prior to their cancer diagnosis. Blood samples were collected pre-vaccination, as well as 2, 4-6, and 8-12 weeks after vaccination. Healthy children who were fully vaccinated enrolled as controls. Clinical data and complete blood counts around time of vaccination were collected. To study B- and T-cell immunity, we measured neutralizing antibodies by enzyme-linked immunoassay and interferon gamma secretion by enzyme-linked immunospot, respectively. RESULTS: Twenty-six patients enrolled on study, for which 11 were evaluable oncology patients and seven were healthy controls. Adequate B-cell response was seen in 36.4% of patients, and adequate T-cell response in 77.8% of patients. Numbers were too small to detect differences based on malignancy type. There was no differences in immunity based on absolute lymphocyte count (ALC) or intensity of therapy. CONCLUSION: Pediatric oncology patients have a suboptimal immune response to SARS-CoV-2 vaccination. Booster doses will be imperative to provide optimal protection against COVID-19; however, blood counts may not be a useful guide to optimize the time of administration.
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COVID-19 , Neoplasias , Criança , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Oncologia , Anticorpos Neutralizantes , Neoplasias/terapia , Vacinação , Anticorpos AntiviraisRESUMO
Polycyclic aromatic hydrocarbons (PAHs) associated with indoor PM pose a high risk to human health because of their toxicity. A total of 160 daily samples of indoor PM2.5 and PM0.1 were collected in Hanoi and analysed for 15 PAHs. In general, the concentrations of carcinogenic PAHs (car-PAHs) accounted for 21% ± 2%, 19.1% ± 2%, and 26% ± 3% of the concentrations of 15 PAHs in PM2.5, PM0.1-2.5, and PM0.1, respectively. Higher percentages of car-PAHs were found in smaller fractions (PM0.1), which can be easily deposited deep in the pulmonary regions of the human respiratory tract. The concentrations of 15 PAHs were higher in winter than in summer. The most abundant PAH species were naphthalene and phenanthrene, accounting for 11%-21% and 19%-23%, respectively. The PAH content in PM0.1 was almost twice as high as those in PM2.5 and PM0.1-2.5. Principal component analysis found that vehicle emissions and the combustion of biomass and coal were the main outdoor sources of PAHs, whereas indoor sources included cooking activities, the combustion of incense, scented candles, and domestic uses in houses. According to the results, 60%-90% of the PM0.1-bound BaP(eq) was deposited in the alveoli region, whereas 63%-75% of the PM2.5-bound BaP(eq) was deposited in head airways (HA), implying that most of the particles deposited in the HA region were PM0.1-2.5. The contributions of dibenz[a,h]anthracene and benzo[a]pyrene were dominant and contributed from 36% to 51% and 31%-50%, respectively, to the carcinogenic potential, whereas benzo[a]pyrene contributed from 30% to 49% to the mutagenic potential for both size fractions. The incremental lifetime cancer risk, simulated by Monte Carlo simulation, was within the limits set by the US EPA, indicating an acceptable risk for the occupants. These results provide an additional scientific basis for protecting human health from exposure to indoor PAHs.
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Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Material Particulado/análise , Poluentes Atmosféricos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental , Benzo(a)pireno/análise , Medição de Risco , ChinaRESUMO
Free-living amoebae (FLA) rarely cause human infections but can invoke fatal infections in the central nervous system (CNS). No consensus treatment has been established for FLA infections of the CNS, emphasizing the urgent need to discover or develop safe and effective drugs. Flavonoids, natural compounds from plants and plant-derived products, are known to have antiprotozoan activities against several pathogenic protozoa parasites. The anti-FLA activity of flavonoids has also been proposed, while their antiamoebic activity for FLA needs to be emperically determined. We herein evaluated the antiamoebic activities of 18 flavonoids against Naegleria fowleri and Acanthamoeba species which included A. castellanii and A. polyphaga. These flavonoids showed different profiles of antiamoebic activity against N. fowleri and Acanthamoeba species. Demethoxycurcumin, kaempferol, resveratrol, and silybin (A+B) showed in vitro antiamoebic activity against both N. fowleri and Acanthamoeba species. Apigenin, costunolide, (â)-epicatechin, (â)-epigallocatechin, rosmarinic acid, and (â)-trans-caryophyllene showed selective antiamoebic activity for Acanthamoeba species. Luteolin was more effective for N. fowleri. However, afzelin, berberine, (±)-catechin, chelerythrine, genistein, (+)-pinostrobin, and quercetin did not exhibit antiamoebic activity against the amoeba species. They neither showed selective antiamoebic activity with significant cytotoxicity to C6 glial cells. Our results provide a basis for the anti-FLA activity of flavonoids, which can be applied to develope alternative or supplemental therapeutic agents for FLA infections of the CNS.