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Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future.
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Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.
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Astrócitos , Infecções por Bunyaviridae , Camundongos Knockout , Phlebovirus , Receptor de Interferon alfa e beta , Animais , Astrócitos/virologia , Astrócitos/patologia , Camundongos , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/deficiência , Phlebovirus/genética , Phlebovirus/fisiologia , Phlebovirus/patogenicidade , Infecções por Bunyaviridae/virologia , Infecções por Bunyaviridae/patologia , Infecções por Bunyaviridae/imunologia , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/imunologia , Medula Espinal/virologia , Medula Espinal/patologia , Modelos Animais de Doenças , Neurônios/virologia , Neurônios/patologia , Camundongos Endogâmicos C57BL , Tronco Encefálico/virologia , Tronco Encefálico/patologia , Morte CelularRESUMO
BACKGROUND: Cetobacterium somerae rarely causes infection in humans. Most studies on C. somerae have analyzed its role in the intestinal system of freshwater fish. METHODS: Herein, we report a case of septic shock caused by C. somerae in an elderly patient. RESULTS: Blood culture revealed growth of a gram-negative, rod-shaped anaerobic bacterium, which was identified as C. somerae through MALDI-TOF analyses. Although C. somerae is a resident species in the gut, it can cause systemic infection, which can be fatal. CONCLUSIONS: When C. somerae is identified, consideration should be given to the possibility of the infection originating from the intestinal tract.
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Choque Séptico , Choque Séptico/microbiologia , Choque Séptico/diagnóstico , Humanos , Antibacterianos/uso terapêutico , Masculino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , Idoso , Idoso de 80 Anos ou mais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , FemininoRESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Furthering insights into patients' ADPKD progression could lead to earlier detection, management, and alter the course to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. A retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using differences in eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. Among 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. Using real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.
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Progressão da Doença , Taxa de Filtração Glomerular , Rim Policístico Autossômico Dominante , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Rim/fisiopatologia , Rim/patologia , Falência Renal Crônica/epidemiologiaRESUMO
In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation.
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Implante Coclear , Perda Auditiva , Lactose , Animais , Lactose/análogos & derivados , Lactose/farmacologia , Perda Auditiva/prevenção & controle , Perda Auditiva/tratamento farmacológico , Audição/efeitos dos fármacos , Cóclea/efeitos dos fármacos , Cóclea/metabolismo , Camundongos , Modelos Animais de Doenças , Linhagem Celular , Citocinas/metabolismo , Masculino , Ácidos SiálicosRESUMO
While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Camundongos Transgênicos , Doença de Parkinson , SARS-CoV-2 , Animais , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/virologia , Humanos , COVID-19/patologia , COVID-19/virologia , Doença de Parkinson/patologia , Doença de Parkinson/virologia , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Microglia/patologia , Microglia/metabolismo , Microglia/virologia , Células-Tronco Embrionárias Humanas/metabolismo , Astrócitos/patologia , Astrócitos/virologia , Astrócitos/metabolismo , Encéfalo/patologia , Encéfalo/virologiaRESUMO
Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.
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Melatonina , NF-kappa B , Melatonina/farmacologia , Animais , NF-kappa B/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos , Camundongos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Gradenigo's syndrome, a rare but serious complication of otitis media, encompasses a triad of symptoms including otalgia, facial palsy, and abducens nerve palsy, pointing to the involvement of the petrous apex. This case report presents an 11-year-old boy with an atypical manifestation of Gradenigo's syndrome, characterized by the absence of classic features such as abducens nerve palsy and purulent otorrhea. MRI findings were significant for petrous apicitis extending to Meckel's cave and the cavernous sinus, along with abscess formation and clivus osteomyelitis. The report highlights the critical role of advanced neuroimaging, particularly MRI, in the diagnosis and management of this condition. It underscores the importance of recognizing atypical presentations of Gradenigo's syndrome and the effectiveness of imaging-guided conservative treatment strategies in pediatric otological cases.
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BACKGROUND: Cerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer's disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening. METHODS: We established AD hPSC lines from normal hPSCs by introducing genes that harbor familial AD mutations, and the COs were generated using these hPSC lines. The pathological features of AD, including extensive amyloid-ß (Aß) accumulation, tauopathy, and neurodegeneration, were analyzed using enzyme-linked immunosorbent assay, Amylo-Glo staining, thioflavin-S staining, immunohistochemistry, Bielschowsky's staining, and western blot analysis. RESULTS: The AD COs exhibited extensive Aß accumulation. The levels of paired helical filament tau and neurofibrillary tangle-like silver deposits were highly increased in the AD COs. The number of cells immunoreactive for cleaved caspase-3 was significantly increased in the AD COs. In addition, treatment of AD COs with BACE1 inhibitor IV, a ß-secretase inhibitor, and compound E, a γ-secretase inhibitor, significantly attenuated the AD pathological features. CONCLUSION: Our model effectively recapitulates AD pathology. Hence, it is a valuable platform for understanding the mechanisms underlying AD pathogenesis and can be used to test the efficacy of anti-AD drugs.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Organoides , Células-Tronco Pluripotentes , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Organoides/metabolismo , Organoides/patologia , Células-Tronco Pluripotentes/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Proteínas tau/metabolismo , Proteínas tau/genética , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/genética , Encéfalo/metabolismo , Encéfalo/patologia , Modelos BiológicosRESUMO
Scholarship on impunity has centered around quantifiable prosecutions related to criminal acts that often occur outside of the workplace. We offer insights into the psychological experience of impunity by shifting the focus to organizational settings and embedding impunity within discussions of workplace misconduct. We distinguish between (a) perceived personal impunity, which reflects employees' belief that they will not face punishment for their own misconduct; and (b) perceived contextual impunity, which reflects employees' belief that their organization will not punish employees for their misconduct. We develop and validate measures for each impunity perception and establish a preliminary nomological network by investigating factors that influence each perception and their relationship with workplace misconduct. Consequently, we offer nuanced insights into how distinct impunity perceptions result in workplace misconduct relative to other established predictors. Our perceived workplace impunity measures provide a valuable tool for assessing impunity perceptions and predicting instances of misconduct. In addition, they offer practical insights into impunity's functions within organizations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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To predict the apparent total tract digestibility (ATTD) of crude protein (CP) in dogs we developed an in vitro system using an in vitro digestion method and a statistical analysis. The experimental diets used chicken meat powder as the protein source, with CP levels of 20% (22.01%, analyzed CP value as dry-based), 30% (31.35%, analyzed CP value as dry-based), and 40% (41.34%, analyzed CP value as dry-based). To simulate in vivo digestive processes a static in vitro digestion was performed in two steps; stomach and small intestine. To analyze ATTD the total fecal samples were collected in eight neutered beagle dogs during the experimental period. CP digestibility was calculated by measuring CP levels in dog food, in vitro undigested fraction, and dog feces. In result, CP digestibility at both in vivo and in vitro was increased with increasing dietary CP levels. To estimate in vivo digestibility the co-relation of in vivo ATTD and in vitro digestibility was investigated statistically and a regression equation was developed to predict the CP ATTD (% = 2.5405 × in vitro CP digestibility (%) + 151.8). The regression equation was evaluated its feasibility by using a commercial diet. The predicted CP digestibility which was calculated by the regression equation showed high index of similarity (100.16%) with that of in vivo in dogs. With that, it would be a feasible non-animal method to predict in vivo CP digestibility by using in vitro digestion method and the proposed linear regression equation in adult dogs.
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Objective: To investigate the association of mental and oral health with the health-related quality of life (HRQOL) in patients with cancer and cancer survivors. Methods: This cross-sectional study involved 1643 patients with cancer and 1628 individuals who survived cancer (aged ≥ 19 years) using data from the 2005-2018 Korean National Health and Nutrition Examination Survey. The data were analyzed using SAS survey procedures (version 9.4), t-tests, χ2 test, and multiple regression. Results: Regarding differences in mental and oral health factors by group, the results revealed significant differences between depression, suicidal ideation, subjective oral health, chewing problems, and speaking problems due to oral issues. The HRQOL of patients with cancer was lower than that of cancer survivors. The factors influencing HRQOL in both patients with cancer and cancer survivors were education status, economic activity, subjective health, suicidal ideation, and speaking problems due to oral issues. HRQOL was also associated with depression in patients with cancer. Conclusions: Patients with cancer had a lower HRQOL than cancer survivors. The two groups of patients showed significant differences in the factors associated with HRQOL. Therefore, customized health programs and policies should be developed and implemented for each group to improve their QOL.
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BACKGROUND: This study analyzed the demographic characteristics of patients with facial palsy who were treated using either dynamic or static procedures. This study aimed to compare the frequency of procedure implementation and age distribution between the two groups. METHODS: This study retrospectively analyzed the medical records of patients treated for facial palsy at a single institution from 2014 to 2022. Among cases included in our study, dynamic procedures involved cross-facial nerve graft and latissimus dorsi or gracilis muscle flap transfer. Static procedures included gold weight insertion, canthopexy, browlift, and thread lift/static slings. RESULTS: Among the 31 patients included in our study, eight (25.8%) incorporated dynamic techniques, and the average age of patients was 44.75 years (range, 24-68 years) with a male to female ratio of 1:4. The remaining 23 patients (74.2%) underwent a static procedure, of which the average age was 59.17 years (range, 23-81 years) which was statistically significantly higher than the average age of 44.75 of dynamic patients (p= 0.013). Regarding the timing of treatment after diagnosis, no patient underwent dynamic procedures more than 20 years after initial diagnosis. A greater diversity in the timing of treatment was observed in the static group. All patients who underwent dynamic procedures were treated using static procedures during the study period. CONCLUSION: Because aesthetics-based static techniques are typically quick outpatient procedures that can be performed under local anesthesia, our study shows that these are often preferred treatments for all age groups, especially for debilitated or older patients. Further research is required to investigate the long-term functional outcomes of these surgical techniques in a wider population of patients.
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Educating primary care physicians about blood donation and transfusion is critical. The Division of Hematology and Oncology at Soonchunhyang University Seoul Hospital in Korea introduced an on-site educational program termed the Blood Donation Center Visiting Program in the clerkship education for final-year medical students. We evaluated the educational outcomes and changes in perception among medical students after the Blood Donation Center Visiting Program based on a survey. The program was implemented from 2021 to 2023. As part of the program, students visited a blood donation center each week, one group at a time. They gained practical knowledge about the blood donation process, and some students actively participated in blood donation. After the program, 287 students were eligible for an online survey of the program, of whom 203 participated in the survey. Among the 203 students, 126 (62.1%) donated blood during their visit to the blood donation center as part of the program, and 88.7% of the students reported an increase (from 71.4% to 90.1%) in their knowledge and willingness to donate blood. The on-site educational Blood Donation Center Visiting Program appears to have generated positive changes in perceptions among students and enhanced their knowledge about blood donation.
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Doadores de Sangue , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Doadores de Sangue/psicologia , Conhecimentos, Atitudes e Prática em Saúde , República da Coreia , Percepção , Feminino , Masculino , Adulto Jovem , Doação de SangueRESUMO
Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proteínas de Homeodomínio , Neurônios , Fatores do Domínio POU , Fatores de Transcrição de Fator Regulador X , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Perfilação da Expressão Gênica , Regiões Promotoras Genéticas , RNA-Seq , Diferenciação Celular , Proteínas de Homeodomínio/genética , Fatores do Domínio POU/genética , Fatores de Transcrição de Fator Regulador X/genéticaRESUMO
Early diagnosis of Alzheimer's disease is crucial to stall the deterioration of brain function, but conventional diagnostic methods require complicated analytical procedures or inflict acute pain on the patient. Then, label-free Surface-enhanced Raman spectroscopy (SERS) analysis of blood-based biomarkers is a convenient alternative to rapidly obtain spectral information from biofluids. However, despite the rapid acquisition of spectral information from biofluids, it is challenging to distinguish spectral features of biomarkers due to interference from biofluidic components. Here, we introduce a deep learning-assisted, SERS-based platform for separate analysis of blood-based amyloid ß (1-42) and metabolites, enabling the diagnosis of Alzheimer's disease. SERS substrates consisting of Au nanowire arrays are fabricated and functionalized in two characteristic ways to compare the validity of different Alzheimer's disease biomarkers measured on our SERS system. The 6E10 antibody is immobilized for the capture of amyloid ß (1-42) and analysis of its oligomerization process, while various self-assembled monolayers are attached for different dipole interactions with blood-based metabolites. Ultimately, SERS spectra of blood plasma of Alzheimer's disease patients and human controls are measured on the substrates and classified via advanced deep learning techniques that automatically extract informative features to learn generalizable representations. Accuracies up to 99.5% are achieved for metabolite-based analyses, which are verified with an explainable artificial intelligence technique that identifies key spectral features used for classification and for deducing significant biomarkers.
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Doença de Alzheimer , Técnicas Biossensoriais , Aprendizado Profundo , Nanopartículas Metálicas , Humanos , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Inteligência Artificial , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , BiomarcadoresRESUMO
BACKGROUND: Label-free surface-enhanced Raman spectroscopy (SERS)-based metabolic profiling has great potential for early cancer diagnosis, but further advancements in analytical methods and clinical evidence studies are required for clinical applications. To improve the cancer diagnostic accuracy of label-free SERS spectral analysis of complex biological fluids, it is necessary to obtain specifically enhanced SERS signals of cancer-related metabolites present at low concentrations. RESULTS: This study presents a novel 3D SERS sensor, comprising a surface-carbonized silver nanowire (AgNW)-stacked filter membrane, alongside an optimized urine/methanol/chloroform extraction technique, which specifically changes the molecular adsorption and orientation of aromatic metabolites onto SERS substrates. By analyzing the pretreated urine samples on the surface-carbonized AgNW 3D SERS sensor, distinct and highly enhanced SERS peaks derived from semi-polar aromatic metabolites were observed for pancreatic cancer and prostate cancer samples compared with normal controls. Urine metabolite analysis using SERS fingerprinting successfully differentiated pancreatic cancer and prostate cancer groups from normal control group: normal control (n = 56), pancreatic cancer (n = 40), and prostate cancer (n = 39). SIGNIFICANCE AND NOVELTY: We confirmed the clinical feasibility of performing fingerprint analysis of urinary metabolites based on the surface-carbonized AgNW 3D SERS sensor and methanol/chloroform extraction for noninvasive cancer screening. This technology holds potential for large-scale screening owing to its high accuracy, and cost effective, simple and rapid detection method.
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Nanopartículas Metálicas , Nanofios , Neoplasias Pancreáticas , Neoplasias da Próstata , Masculino , Humanos , Análise Espectral Raman/métodos , Detecção Precoce de Câncer , Prata/química , Clorofórmio , Metanol , Nanopartículas Metálicas/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) remains a significant global health concern, and targeting inflammation has emerged as a promising approach for its prevention and treatment. Medicinal plants and phytochemicals have garnered attention for their potential efficacy against inflammation with minimal toxicity. Osmanthus fragrans var. aurantiacus Makino (O. fragrans) has a history of traditional use in Korea and China in treating various inflammation-related conditions, but its potential use for CRC has not been uncovered. AIM OF THE STUDY: This study aims to explore the potential anti-proliferative and pro-apoptotic properties of O. fragrans, focusing on its impact on CRC treatment. By investigating O. fragrans, we aim to uncover its anti-proliferative and apoptotic effects in human CRC cells, potentially paving the way for effective and well-tolerated therapeutic strategies for CRC patients. MATERIALS AND METHODS: Ethanol (EtOH) extracts of O. fragrans leaf and flower, along with specific fractions (n-hexane, ethyl acetate (EtOAc), n-butanol, and the aqueous residue) were evaluated for their anti-proliferative effects in human CRC cells using MTT assays, and compared to normal colon cells. Mechanistic insights and chemical profiling were obtained through flow cytometry, colorimetric assays, western blotting, and molecular docking, and high-performance liquid chromatography (HPLC) system. RESULTS: Both flower and leaf EtOH extracts of O. fragrans exhibited significant anti-proliferative effects in human CRC cells, with the leaf extract demonstrating higher potency. The EtOAc fraction from the leaf extract displayed the strongest anti-CRC cell proliferative effects while no cytotoxic effects in normal colon cells. Chemical profiling of these fractions identified triterpenoids as significant components in the EtOAc fractions. The leaf EtOAc fraction caused cell cycle arrest and apoptosis, accompanied by elevating intracellular reactive oxygen species and mitochondrial dysfunction in CRC cells. Additionally, it inhibited NF-κB and ERK1/2 signaling, leading to reduced COX2 expression. Notably, two triterpenoids isolated from the leaf EtOAc fraction, maslinic acid and corosolic acid, displayed potent anti-cancer activity in CRC cells without affecting normal colon cells. Corosolic acid exhibited a strong binding affinity to COX2 and reduced its expression, supporting its role in the anti-inflammatory and anti-cancer effects. CONCLUSIONS: Our findings suggest that O. fragrans, particularly its triterpenoid-rich EtOAc fraction, holds promise as a novel therapeutic agent for CRC prevention and therapy. These results provide valuable insights into the potential application of O. fragrans and its bioactive compounds in combating CRC.
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Acetatos , Neoplasias Colorretais , Triterpenos , Humanos , NF-kappa B , Extratos Vegetais/uso terapêutico , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Inflamação/tratamento farmacológico , Etanol/farmacologia , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológicoRESUMO
South Korea recently shifted its assessment indicator for organic matter in terrestrial environments from chemical oxygen demand (COD) to total organic carbon (TOC) due to the increase in refractory organic carbon levels. However, in the marine environment, where the inflow of refractory organic matter is also on the rise, COD is still used in some instances to assess organic pollution in contaminated areas. Our findings reveal that the main source of dissolved organic carbon (DOC) is terrestrial-derived refractory organic carbon, which enters through nearby wastewater treatment plant (WWPT) outlets. The low oxidation efficiency of COD to TOC (approximately 4 %) prevents it from being an accurate measure of terrestrial-derived refractory DOC. Contrasting results were observed when comparing the organic pollution index (OPI), which we calculated using TOC, with the currently employed water quality index (WQI) for ocean water quality evaluation, particularly in areas influenced by WWPTs. This discrepancy arises because the WQI primarily evaluates autochthonous organic carbon through chlorophyll measurements, whereas the OPI incorporates both autochthonous and allochthonous organic carbon through TOC measurements. Our findings demonstrate that TOC can effectively replace COD as an organic pollution indicator in marine environments.
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BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).