RESUMEN
The interplay of onco-immunology and kidney transplantation heralds a transformative era in medical science. This integration, while promising, presents significant challenges. Chief among these is the dichotomy of immunosuppression-boosting immunity against malignancies while suppressing it for graft survival. Additionally, limited clinical data on novel therapies, genetic variations influencing responses, economic concerns, and the narrow therapeutic window for post-transplant malignancies necessitate strategic addressal. Conversely, opportunities abound, including personalized immune monitoring, targeted therapies, minimized immunosuppression, and improved patient quality of life. Emphasizing collaborative research and interdisciplinary cooperation, the merging of these fields offers the potential for enhanced graft survival and reduced post-transplant malignancy risks. As we harness modern technology and promote patient-centric care, the vision for the future of kidney transplantation becomes increasingly hopeful, paving the way for more personalized and effective treatments. The article aims to elucidate the critical challenge of balancing immunosuppression to simultaneously combat malignancies and ensure graft survival. It addresses the scarcity of clinical data on novel therapies, the impact of genetic variations on treatment responses, and the economic and therapeutic concerns in managing post-transplant malignancies. Furthermore, it explores the opportunities precision medicine offers, such as personalized immune monitoring, targeted therapies, and reduced immunosuppression, which could significantly improve patient outcomes. Highlighting the importance of collaborative research and interdisciplinary efforts, the article seeks to demonstrate the potential for enhanced graft survival and reduced post-transplant malignancy risks. By leveraging modern technology and prioritizing patient-centric care, it envisions a future where kidney transplantation is more personalized and effective, offering hope for advancements in this field.
RESUMEN
Breast cancer presents a significant global health challenge with rising incidence rates worldwide. Despite current efforts, it remains inadequately controlled. Functional foods, notably tempeh, have emerged as promising candidates for breast cancer prevention and treatment due to bioactive peptides and isoflavones exhibiting potential anticancer properties by serving as antioxidants, inducing apoptosis, and inhibiting cancer cell proliferation. This study integrates pharmacoinformatics and cellular investigations (i.e., a multifaceted approach) to elucidate the antioxidative and anti-breast cancer properties of tempeh-derived isoflavones. Methodologies encompass metabolomic profiling, in silico analysis, antioxidant assays, and in vitro experiments. Daidzein and genistein exhibited potential therapeutic options for breast cancer treatment and as antioxidant agents. In vitro studies also supported their efficacy against breast cancer and their ability to scavenge radicals, particularly in soy-based tempeh powder (SBT-P) and its isoflavone derivatives. Results have demonstrated a significant downregulation of breast cancer signaling proteins and increased expression of miR-7-5p, a microRNA with tumor-suppressive properties. Notably, the LD50 values of SBT-P and its derivatives on normal breast cell lines indicate their potential safety, with minimal cytotoxic effects on MCF-10A cells compared to control groups. The study underscores the favorable potential of SBT-P as a safe therapeutic option for breast cancer treatment, warranting further clinical exploration.
RESUMEN
Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, and various types of cancer. Therefore, it is critical to suppress cancer progression and proliferation. Ferroptosis can be triggered in cancer cells and some normal cells by synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or clinical pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, and some have been therapeutically used as dietary additives or pharmaceutical agents against various malignancies. The fact that natural products have multiple targets and minimal side effects has led to notable advances in anticancer research. Research has indicated that ferroptosis can also be induced by natural compounds during cancer treatment. In this review, we focused on the most recent developments in emerging molecular processes and the significance of ferroptosis in cancer. To provide new perspectives on the future development of ferroptosis-related anticancer medications, we also provide a summary of the implications of natural phytochemicals in triggering ferroptosis through ROS production and ferritinophagy induction in a variety of malignancies.
Asunto(s)
Antineoplásicos , Ferroptosis , Neoplasias , Humanos , Especies Reactivas de Oxígeno/metabolismo , Hierro/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
The silkworm (Bombyx mori) has long been valued food and feed in East Asia for its abundant nutritional and medicinal attributes, conversely, it can elicit allergic responses in susceptible individuals. Therefore, the development of silkworm detection method is required to avert allergenic incidents. In this study, two methodologies, tandem mass spectrometry (LC-MS/MS) and real-time PCR, were developed to achieve effective silkworm detection. These methods exhibited exceptional sensitivity in identifying silkworm presence in processed foods. Furthermore, model cookies spiked with silkworm were used to validate the sensitivities of LC-MS/MS (0.0005%) and real-time PCR (0.001%). Overall, these techniques were useful for trace silkworm detection in food products; therefore, they may help prevent allergic reactions. To the best of our knowledge, this study represents the first comparison of LC-MS/MS and real-time PCR methods for silkworm detection, marking an important contribution to the field. Data are available from ProteomeXchange under identifier PXD042494.
Asunto(s)
Bombyx , Hipersensibilidad , Animales , Humanos , Bombyx/genética , Bombyx/química , Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas en Tándem , Cromatografía Liquida , Reacción en Cadena en Tiempo Real de la Polimerasa , Alérgenos/genéticaRESUMEN
The host-seeking behavior of mosquitoes have long been established to be primarily odor-mediated. In this process, olfactory receptors (Ors) play a critical role. 1-Octen-3-ol is a common volatile compound that is attractive to hematophagous arthropods such as mosquitos. The olfactory receptor 8 (AaOr8) on the tip of the stylet and maxillary palp of Aedes aegypti is tuned to 1-octen-3-ol, which is required for mosquitoes to quickly find blood vessels from a vertebrate host. However, little is known about the interaction of AaOr8 with 1-octen-3-ol which was studied in vivo and in silico in this study. The molecular binding poses and energies between ligands and the receptor were investigated. Three mutants of AaOr8 were cloned and compared with in vivo calcium imaging utilizing heterologous expression systems. As a result, our findings imply that a genetic disruption including targeted modification of Ors genes may be used to reduce mosquito bites.
Asunto(s)
Aedes , Neuronas Receptoras Olfatorias , Receptores Odorantes , Animales , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Aedes/metabolismo , Neuronas Receptoras Olfatorias/metabolismo , Octanoles/químicaRESUMEN
Polymeric immunoglobulin receptor (pIgR) mediates the transfer of polymeric immunoglobulin to protect organisms and is one of the most important mucosal effectors. In this study, the developmental stage- and tissue-specific expression of pIgR were observed before virus inoculation in olive flounder. pIgR was gradually expressed until the formation of immune tissue, exhibiting high expression in the late juvenile period; thereafter, pIgR expression gradually decreased and exhibited high expression in the spleen and skin. Moreover, pIgR expression after viral hemorrhagic septicemia virus infection was high in the kidney and spleen tissues at high density and low at low density. The results of this study can provide a basis for future studies on breeding density, virus expression, and immune system studies in fish.
RESUMEN
Though Morusin is known to induce apoptotic, antiprolifertaive, and autophagic effects through several signaling pathways, the underlying molecular mechanisms of Morusin still remain unclear until now. To elucidate antitumor mechanism of Morusin, cytotoxicity assay, cell cycle analysis, Western blotting, TUNEL assay, RNA interference, immunofluorescense, immunoprecipitation, reactive oxygen species (ROS) measurement, and inhibitor study were applied in this study. Morusin enhanced cytotoxicity, increased the number of TUNEL positive cells, sub-G1 population and induced the cleavages of PARP and caspase3, attenuated the expression of HK2, PKM2, LDH, c-Myc, and Forkhead Box M1 (FOXM1) along with the reduction of glucose, lactate, and ATP in DU145 and PC3 cells. Furthermore, Morusin disrupted the binding of c-Myc and FOXM1 in PC-3 cells, which was supported by String and cBioportal database. Notably, Morusin induced c-Myc degradation mediated by FBW7 and suppressed c-Myc stability in PC3 cells exposed to MG132 and cycloheximide. Also, Morusin generated ROS, while NAC disrupted the capacity of Morusin to reduce the expression of FOXM1, c-Myc, pro-PARP, and pro-caspase3 in PC-3 cells. Taken together, these findings provide scientific evidence that ROS mediated inhibition of FOXM1/c-Myc signaling axis plays a critical role in Morusin induced apoptotic and anti-Warburg effect in prostate cancer cells. Our findings support scientific evidence that ROS mediated inhibition of FOXM1/c-Myc signaling axis is critically involved in apoptotic and anti-Warburg effect of Morusin in prostate cancer cells.
Asunto(s)
Neoplasias de la Próstata , Transducción de Señal , Masculino , Humanos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Apoptosis , Línea Celular Tumoral , Neoplasias de la Próstata/metabolismo , Proliferación Celular , Proteína Forkhead Box M1/metabolismoRESUMEN
Increased ocean temperature due to global warming affects the health and immunity of fish. In this study, juvenile Paralichthys olivaceus were exposed to high temperature after pre-heat (Acute: Acute heat shock at 32 °C, AH-S: Acquired heat shock at 28 °C & short recovery (2 h) and heat shock at 32 °C, AH-L: acquired heat shock at 28 °C and long recovery (2 days), AH-LS: acquired heat shock at 28 °C & long (2 days) + short (2 h) recovery). Heat shock after pre-heat significantly upregulated various immune-related genes, including interleukin 8 (IL-8), c-type lysozyme (c-lys), immunoglobulin M (IgM), Toll-like receptor 3 (tlr3), major histocompatibility complex IIα (mhcIIα) and cluster of differentiation 8α (cd8α) in the liver and brain of P. olivaceus. This study showed pre-exposure to high temperatures below the critical temperature can activate fish immunity and increase tolerance to high temperatures.
Asunto(s)
Enfermedades de los Peces , Lenguado , Animales , Lenguado/genética , Temperatura , Agua , Calor , Peces/genética , Expresión GénicaRESUMEN
Emerging pharmaceutical pollutants pose a threat to both human and environmental health. The removal and monitoring of such pollutants necessitate the use of practical on-site monitoring devices; however, the designs of such devices are underdeveloped. This study involves the fabrication of a low-cost sensor based on barium-incorporated copper oxide (Ba-CuO) for the on-site monitoring of the cytotoxic drug methotrexate (MTRX) in water and sediment samples. The tenorite structure of CuO was slightly enriched with Ba ions at the td sites, distorting the tetrahedron and enhancing its electrochemical properties. Ba-CuO was obtained from Cu(NO3)2 and Ba(OH)2 by a ligand exchange protocol and was characterized using X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray analysis. In addition, the Ba-CuO sensor was tested under various conditions, and it could detect MTRX at concentrations as low as 0.4 nM, with a high sensitivity of 1.3567 µA µM-1 cm-2. On-site monitoring yielded recoveries of greater than 93 % from spiked samples, thus exhibiting excellent reproducibility and stability. Therefore, the developed method is practical and has no matrix effect on the MTRX sensor.
Asunto(s)
Antineoplásicos , Metotrexato , Humanos , Cobre/química , Bario , Reproducibilidad de los Resultados , ÓxidosRESUMEN
Multisystem inflammatory syndrome in adults (MIS-A) is a rare sequelae after coronavirus disease 2019 (COVID-19) that is characterized by fever as well as cardiovascular and gastrointestinal disorders. We present the case of an 80-year-old Korean woman with MIS-A who experienced febrile sensations, dyspnea, and whole body pain for 7 weeks after being diagnosed with COVID-19. Initial evaluation revealed heart failure, left pleurisy, and sensory neuropathy, but no evidence of infectious diseases was found. Her symptoms improved quickly after starting systemic glucocorticoid therapy, and inflammatory marker levels decreased. When treating patients with fever after COVID-19, it is critical to suspect MIS-A as one of the differential diagnoses for timely diagnosis and treatment.
RESUMEN
The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/ E2). We axenically cultured KFA5 and KFA21. We applied approximately 1 × 106 to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4+ interleukin 4+ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.
Asunto(s)
Acanthamoeba , Amoeba , Acanthamoeba/genética , Amoeba/genética , Animales , Líquido del Lavado Bronquioalveolar , Eosinófilos , Inflamación , Ratones , AguaRESUMEN
Tripartite motif-containing (TRIM) proteins are conserved throughout the metazoan kingdom, and the TRIM subset finTRIM is highly diversified in fish. We isolated TRIM16 cDNA, a member of the finTRIM family, from the olive flounder Paralichthys olivaceus (PoTRIM16). PoTRIM16 contained a 1,725-bp coding sequence encoding a 574-amino acid polypeptide, which in turn contained a really interesting new gene (RING) finger domain, B-box-type zinc finger (B-BOX), nuclease SbcCD subunit C (SbcC), structural maintenance of chromosome (SMC prok B), and stonustoxin (SNTX) subunit alpha (SPRY-PRY-SNTX). Multiple alignment of related sequences revealed that PoTRIM16 showed 86.63-97.40% identity with fish orthologues, and a phylogenetic tree was constructed of vertebrates. PoTRIM16 mRNA was detected in all tissues examined; levels were highest in the eye and ovary. PoTRIM16 mRNA expression was investigated during early development. Under VHSV infection, PoTRIM16 mRNA was downregulated in the liver of P. olivaceus. This is the first study to characterize fish-specific finTRIM in P. olivaceus, which may play a role in the immune response against virus infection.
Asunto(s)
Enfermedades de los Peces , Lenguado , Novirhabdovirus , Animales , Femenino , Novirhabdovirus/fisiología , Filogenia , ARN Mensajero/metabolismoRESUMEN
Shrimp is one of the most valuable aquaculture species globally, and the most internationally traded seafood product. Consequently, shrimp aquaculture practices have received increasing attention due to their high value and levels of demand, and this has contributed to economic growth in many developing countries. The global production of shrimp reached approximately 6.5 million t in 2019 and the shrimp aquaculture industry has consequently become a large-scale operation. However, the expansion of shrimp aquaculture has also been accompanied by various disease outbreaks, leading to large losses in shrimp production. Among the diseases, there are various viral diseases which can cause serious damage when compared to bacterial and fungi-based illness. In addition, new viral diseases occur rapidly, and existing diseases can evolve into new types. To address this, the review presented here will provide information on the DNA and RNA of shrimp viral diseases that have been designated by the World Organization for Animal Health and identify the latest shrimp disease trends.
Asunto(s)
Penaeidae , Virosis , Animales , Acuicultura , Alimentos Marinos , Mariscos , Virosis/veterinariaRESUMEN
Reducing the time to diagnose COVID-19 helps to manage insufficient isolation-bed resources and adequately accommodate critically ill patients. There is currently no alternative method to real-time reverse transcriptase polymerase chain reaction (RT-PCR), which requires 40 cycles to diagnose COVID-19. We propose a deep learning (DL) model to improve the speed of COVID-19 RT-PCR diagnosis. We developed and tested a DL model using the long short-term memory method with a dataset of fluorescence values measured in each cycle of 5810 RT-PCR tests. Among the DL models developed here, the diagnostic performance of the 21st model showed an area under the receiver operating characteristic (AUROC), sensitivity, and specificity of 84.55%, 93.33%, and 75.72%, respectively. The diagnostic performance of the 24th model showed an AUROC, sensitivity, and specificity of 91.27%, 90.00%, and 92.54%, respectively.
Asunto(s)
Prueba de Ácido Nucleico para COVID-19 , COVID-19 , Aprendizaje Profundo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/genética , Humanos , Sensibilidad y EspecificidadRESUMEN
This study examined factors associated with willingness to engage in communication behaviors related to climate change advocacy. Data were collected as part of an online, longitudinal US study beginning in March 2020. Outcomes included willingness to post materials online, contact state legislators, and talk with peers about climate change. Covariates included climate change-related social norms, avoidance of climate change information, and perceptions of the future impact of climate change. A minority of the 586 respondents (23%) reported regular conversations about climate change, while approximately half of the respondents reported willingness to discuss climate change with peers (58%), post materials online (47%), and contact state legislators (46%). Strong predictors of willingness to engage in each climate change communications behaviors included climate change social norms, not avoiding climate change information, and believing that climate change will have a negative impact on the future. Findings indicate the importance of designing programs to foster increased climate change communications in order to promote community-level climate change advocacy norms.
Asunto(s)
Cambio Climático , Normas Sociales , Comunicación , Grupo ParitarioRESUMEN
BACKGROUND: Cerebral ischemia and its reperfusion injury facilitate serious neurodegenerative diseases such as dementia due to cell death; however, there is currently no treatment for it. Reactive oxygen species is one of the many factors that induce and worsen the development of such diseases, and it can be targeted by hydrogen treatment. This study examined the effect of molecular hydrogen in cerebral ischemia-reperfusion injury, which is emerging as a novel therapeutic agent for various diseases. METHODS: Ischemia-reperfusion injury was generated through bilateral common carotid artery occlusion in C57BL/6 mice. The test group received hydrogen-rich water orally during the test period. To confirm model establishment and the effect of hydrogen treatment, behavioural tests, biochemical assays, immunofluorescence microscopy, and cytokine assays were conducted. RESULTS: Open field and novel object recognition tests revealed that the hydrogen-treated group had improved cognitive function and anxiety levels compared to the nontreated group, while hematoxylin and eosin stain showed abundant pyknotic cells in a model mouse brain, and this was attenuated in the hydrogen-treated mouse brain. Total antioxidant capacity and thiobarbituric acid reactive substance assays revealed that hydrogen treatment induced antioxidative effects in the mouse brain. Immunofluorescence microscopy revealed attenuated apoptosis in the striatum, cerebral cortex, and hippocampus of hydrogen-treated mice. Western blotting showed that hydrogen treatment reduced Bax and TNFα levels. Finally, cytokine assays showed that IL-2 and IL-10 levels significantly differed between the hydrogen-treated and nontreated groups. CONCLUSION: Hydrogen treatment could potentially be a future therapeutic strategy for ischemia and its derived neurodegenerative diseases by improving cognitive abilities and inducing antioxidative and antiapoptotic effects. Hydrogen treatment also decreased Bax and TNFα levels and induced an anti-inflammatory response via regulation of IL-2 and IL-10. These results will serve as a milestone for future studies intended to reveal the mechanism of action of molecular hydrogen in neurodegenerative diseases.
Asunto(s)
Cognición/efectos de los fármacos , Óxido de Deuterio/farmacología , Daño por Reperfusión/tratamiento farmacológico , Agua/farmacología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Cognición/fisiología , Óxido de Deuterio/metabolismo , Modelos Animales de Enfermedad , Hidrógeno/química , Hidrógeno/farmacología , Isquemia/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Especies Reactivas de Oxígeno , Daño por Reperfusión/metabolismo , Agua/químicaRESUMEN
While the majority of the American public believe climate change is occurring and are worried, few are engaged in climate change action. In this study, we assessed factors associated with the level of willingness to engage in climate change actions using an online, longitudinal US study of adults. Climate change action outcomes included the level of willingness to post materials online, take political actions, talk with peers about climate change, and donate to or help an organization. Predictors included climate change attitudes, environmental attitudes, political ideology, political party affiliation, and demographic variables. Most (72%) of the 644 respondents only talked about climate change with peers a few times a year or less, though 65% were very or extremely worried about climate change. Many respondents indicated a willingness to do somewhat or a lot more, from 38% willing to talk to peers to 25% for willing to take political actions. In multinomial regression models, the Climate Change Concern scale was strongly and consistently associated with willingness to engage in climate change action. These findings indicate a need to both identify those who are willing to act and finding activities that fit with their interests and availability.
Asunto(s)
Cambio Climático , Política , Actitud , Organizaciones , Estados UnidosRESUMEN
BACKGROUND: Given the increased fluconazole resistance (FR) among Candida isolates, we assessed the suitability of disk diffusion susceptibility testing (DDT) for the early detection of FR using well-characterized Candida isolates. METHODS: In total, 188 Candida isolates, including 66 C. albicans (seven Erg11 mutants), 69 C. glabrata (33 Pdr1 mutants), 29 C. parapsilosis (15 Erg11 mutants), and 24 C. tropicalis (eight Erg11 mutants) isolates, were tested in this study. FR was assessed using DDT according to the standard CLSI M44-ED3 method, except that two cell suspensions, McFarland 0.5 (standard inoculum) and 2.5 (large inoculum), were used, and the inhibition zones were read at 2-hour intervals from 10 hours to 24 hours. RESULTS: DDT results for the standard inoculum were readable after 14 hours (C. albicans, C. glabrata, and C. tropicalis) and 20 hours (C. parapsilosis) for >95% of the isolates, whereas the results for the large inoculum were readable after 12 hours (C. glabrata and C. tropicalis), 14 hours (C. albicans), and 16 hours (C. parapsilosis) for >95% of the isolates. Compared with the results produced using the CLSI M27-ED4 broth microdilution method, the first readable results from the DDT method for each isolate exhibited an agreement of 97.0%, 98.6%, 72.4%, and 91.7% for the standard inoculum and 100%, 98.6%, 96.6%, and 95.8% for the large inoculum for C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis, respectively. CONCLUSIONS: DDT using large inoculum may detect FR rapidly and reliably in the four most common Candida species.
Asunto(s)
Candida , Fluconazol , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida/genética , Candida albicans/genética , Farmacorresistencia Fúngica , Fluconazol/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: The olive flounder (Paralichthys olivaceus) is a saltwater fish, which is valuable to the economy. The olive flounder strives to adapt to environmental stressors through physiological, biochemical, and transcriptional responses. The rise in water temperature threatens the growth, development, reproduction, and survival of olive flounder. Each organ in the olive flounder can differentially respond to heat stress. OBJECTIVES: The purpose of this study is to investigate organ-specific transcriptional changes in olive flounder tissues during heat stress. METHODS: In this study, transcriptome dynamics of the gill, liver, and muscle of olive flounder to acute or chronic heat stress were investigated. RESULTS: Principal component analysis plotting revealed that the transcriptome of each organ is quite separated. K-means clustering, gene ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed the differential transcriptome responses of each organ to heat stress. Heat stress commonly affects the pathways involved in the correct protein folding, DNA repair, and cell cycle. CONCLUSION: Our results may provide a valuable molecular basis of heat acclimation in fishes.