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Sinergismo Farmacológico , Leucemia Mieloide Aguda , Mutación , Inhibidores de Proteínas Quinasas , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Quinasa Activadora de Quinasas Ciclina-Dependientes , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
The ground state of a one-dimensional spin- 1 2 uniform antiferromagnetic Heisenberg chain (AfHc) is a Tomonaga-Luttinger liquid which is quantum-critical with respect to applied magnetic fields up to a saturation field µ 0 H s beyond which it transforms to a fully polarized state. Wilson ratio has been predicted to be a good indicator for demarcating these phases [Phys. Rev. B 96, 220401 (2017)]. From detailed temperature and magnetic field-dependent magnetization, magnetic susceptibility and specific heat measurements in a metalorganic complex and comparisons with field theory and quantum transfer matrix method calculations, the complex was found to be a very good realization of a spin- 1 2 AfHc. Wilson ratio obtained from experimentally obtained magnetic susceptibility and magnetic contribution of specific heat values was used to map the magnetic phase diagram of the uniform spin- 1 2 AfHc over large regions of phase space demarcating Tomonaga-Luttinger liquid, saturation field quantum critical, and fully polarized states. Luttinger parameter and spinon velocity were found to match very well with the values predicted from conformal field theory.
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BACKGROUND: The increasing population of cancer survivors poses a significant challenge for healthcare systems globally, necessitating comprehensive post-treatment care to address diverse physical, psychological, and social needs. OBJECTIVE: This systematic review aims to synthesize and critically evaluate the current evidence concerning the unmet needs for nursing services among cancer survivors, spanning various dimensions of survivorship care. METHODS: A systematic search was conducted across major databases, including PubMed, CINAHL, and PsycINFO, to identify relevant studies investigating the unmet needs and health-related quality-of-life (HRQOL) of nursing services led by nurses among cancer survivors. The final search update was conducted in June 2024. Unmet needs dimensions were categorized by the biopsychosocial-spiritual framework. RESULTS: Of the 9503 records searched, 18 studies were included. This review revealed mixed findings in the domains of unmet needs and interventions aimed at addressing them. While nurse-led interventions showed promise in addressing physical and daily living needs, outcomes related to psychological and emotional needs varied across studies. Additionally, nurse-led interventions were effective in addressing patient-clinician communication and health system/information needs, although statistical significance was not consistently observed. HRQOL assessments using general and cancer-specific measures yielded mixed findings. CONCLUSIONS: Despite limitations of the risk of bias of included studies and weak study designs for evaluating nurse-led intervention effects for cancer survivors, the findings highlight the potential of nursing practice to significantly contribute to improving unmet needs of physical, psychological, and social perspectives and ultimately improving their HRQOL. However, the impact on the spiritual needs of nursing care services is limited by the low number of studies. IMPLICATIONS FOR CANCER SURVIVORS: By providing comprehensive support and management, nursing practice can enhance post-treatment outcomes and HRQOL for cancer survivors, contributing to more patient-centered and effective care delivery. More rigorous research considering a biopsychosocial-spiritual perspective to help cancer survivors improve HRQOL is needed.
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Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.
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The present study aimed to identify the metabolites associated with the physiological activity of kimchi-derived lactic acid bacteria (LAB). A clear difference was observed between the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging rates when the pyruvate content was high (273.5 ng/µL; radical removal speed 6.50% per min) and the rates when the pyruvate content had decreased (131.9 ng/µL; radical removal speed 3.63% per min). Additionally, the characteristics of LAB antioxidant activity (increase in ABTS radical scavenging activity with reaction time, low level of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity) were similar to those of pyruvate-derived activity. Hydrogen peroxide content (WiKim0124, 2.08 â 0.26; WiKim0121, 0.99 â 0.47; WiKim39, 1.93 â 0.24) and lactate dehydrogenase activity (WiKim0124, 1.53 â 0.00; WiKim0121, 0.73 â 0.01; WiKim39, 1.72 â 0.02) decreased more in heat-killed LAB than in non-heat-killed LAB. Accordingly, this resulted in increased pyruvate content and the inhibitory activity of lipid peroxide production increased by 2-3 times. Our findings indicate that pyruvate is one of the major metabolites regulating LAB physiological activity. PRACTICAL APPLICATION: The safety of utilizing live probiotics remains a topic of debate. To mitigate associated risks, there is a growing interest in non-viable microorganisms or microbial cell extracts for use as probiotics. Various methods can be employed for probiotic inactivation. Heat treatment typically emerges as the preferred choice for inactivating probiotic strains in many instances. The present study shows the distinctions between inactivating lactic acid bacteria (LAB) through heat treatment and non-heat treatment. It may serve as a valuable reference for selecting an appropriate inactivation method for LAB in industrial processes.
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BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy. METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice. RESULTS: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours. CONCLUSIONS: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).
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Esclerosis Amiotrófica Lateral , Interfaces Cerebro-Computador , Disartria , Habla , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/rehabilitación , Calibración , Equipos de Comunicación para Personas con Discapacidad , Disartria/rehabilitación , Disartria/etiología , Electrodos Implantados , Microelectrodos , Cuadriplejía/etiología , Cuadriplejía/rehabilitaciónRESUMEN
BACKGROUND AND OBJECTIVES: This study aimed to analyze the outcomes of Fontan surgery in the Republic of Korea, as there were only a few studies from Asian countries. METHODS: The medical records of 1,732 patients who underwent Fontan surgery in 10 cardiac centers were reviewed. RESULTS: Among them, 1,040 (58.8%) were men. The mean age at Fontan surgery was 4.3±4.2 years, and 395 (22.8%) patients presented with heterotaxy syndrome. According to the types of Fontan surgery, 157 patients underwent atriopulmonary (AP) type; 303, lateral tunnel (LT) type; and 1,266, extracardiac conduit (ECC) type. The overall survival rates were 91.7%, 87.1%, and 74.4% at 10, 20, and 30 years, respectively. The risk factors of early mortality were male, heterotaxy syndrome, AP-type Fontan surgery, high mean pulmonary artery pressure (mPAP) in pre-Fontan cardiac catheterization, and early Fontan surgery year. The risk factors of late mortality were heterotaxy syndrome, genetic disorder, significant atrioventricular valve regurgitation (AVVR) before Fontan surgery, high mPAP in pre-Fontan cardiac catheterization, and no fenestration. CONCLUSIONS: In Asian population with a high incidence of heterotaxy syndrome, the heterotaxy syndrome was identified as the poor prognostic factors for Fontan surgery. The preoperative low mPAP and less AVVR are associated with better early and long-term outcomes of Fontan surgery.
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Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases.
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Carcinoma de Pulmón de Células no Pequeñas , Variación Genética , Genotipo , Poliomavirus de Células de Merkel , Infecciones por Papillomavirus , Humanos , Carcinoma de Pulmón de Células no Pequeñas/virología , Carcinoma de Pulmón de Células no Pequeñas/genética , Femenino , Poliomavirus de Células de Merkel/genética , Poliomavirus de Células de Merkel/aislamiento & purificación , Persona de Mediana Edad , Masculino , Anciano , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , República de Corea/epidemiología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/complicaciones , Papillomaviridae/genética , Papillomaviridae/clasificación , Adulto , Coinfección/virología , Coinfección/epidemiología , Neoplasias Pulmonares/virología , Anciano de 80 o más Años , Prevalencia , ADN Viral/genética , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/complicaciones , Infecciones Tumorales por Virus/epidemiología , Reacción en Cadena de la Polimerasa , Virus del Papiloma HumanoRESUMEN
BACKGROUND: To investigate the clinical treatment status, such as treatment regimen, bleeding events, and drug dose, in patients with hemophilia B in South Korea. METHODS: In this retrospective chart review, data of patients with hemophilia B from eight university hospitals were collected. Demographic and clinical data, treatment data, such as regimen and number of injections, dose of factor IX concentrate, and bleeding data were reviewed. Descriptive analyses were performed with annual data for 2019, 2020, and 2021, as well as the three years consecutively. RESULTS: The medical records of 150 patients with hemophilia B between January 1, 2019, and December 31, 2021, were collected. Among these, 72 (48.0%) were severe, 47 (31.3%) were moderate, and 28 (18.7%) were mild. The results showed approximately two times more patients receiving prophylaxis as those receiving on-demand therapy, with 66.1% of patients receiving prophylaxis in 2019, 64.9% in 2020, and 72.1% in 2021. Annualized bleeding rates were 2.2% (± 3.1) in 2019, 1.8% (± 3.0) in 2020, and 1.8% (± 2.9) in 2021 among patients receiving prophylaxis. For the doses of factor IX concentrate, patients receiving prophylaxis received an average of 41.6 (± 11.9) IU/Kg/Injection in 2019, 45.7 (± 12.9) IU/Kg/Injection in 2020, and 60.1 (± 24.0) IU/Kg/Injection in 2021. CONCLUSIONS: Clinically, prophylaxis is more prevalent than reported. Based on insights gained from current clinical evidence, it is expected that the unmet medical needs of patients can be identified, and physicians can evaluate the status of patients and actively manage hemophilia B using more effective treatment strategies.
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Inkjet printing, a highly promising technique for the cost-effective fabrication of large-scale organic light-emitting devices (OLEDs), typically necessitates the intricate alignment of precisely patterned insulating layers. Recently, we introduced a unique single-step inkjet printing process that produces well-patterned microinlaid spots of functional compounds through insulating polymer layers. This approach exploits lateral phase separation between the solute of functional compounds and the polymer, allowing the simultaneous spatial etching of the polymer and the infilling of the solute using a single inkjet-printed sessile droplet. Here, we demonstrate that the interaction between the solvent and polymer, as well as the solute and polymer, critically determines the precision and efficiency of printing. This is particularly evident when using either the insulating poly(vinylpyridine) isomer of poly(4-vinylpyridine) (P4VP) or poly(2-vinylpyridine) (P2VP) with chloroform as a solvent, which allows for a detailed examination of these interactions based on certain solubility parameters. Micro-Raman spectroscopy reveals that the self-organizing capability of the microinlaid spots with P4VP is superior to that with P2VP. This is due to the fact that P2VP shows higher affinity to the solvent and causes imperfect phase separation as compared to P4VP. As a result, a performance evaluation demonstrates enhanced device performance for inkjet-printed green micro-OLEDs with P4VP, exhibiting a higher external quantum efficiency of 3.3% compared to that of 2.3% achieved with P2VP. These findings elucidate the important roles of solvent-polymer and solute-polymer interactions in the inkjet printing process, leading to interfacial control of inkjet printing technique for the cost-effective production of high-performance and high-resolution micro-OLEDs.
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This study explores a novel and sustainable approach to reusing textile wastewater for irrigation. This is investigated by degrading Evans blue dye, a model azo dye, in wastewater by combining iron oxide predecessor (IOP) catalyst with gaseous species generated by multi-electrode cylindrical plasma device (MCPD). Analysis of IOP-plasma gaseous species revealed the generation of different types of reactive oxygen species in solution which were responsible for degradation of model dye. Key factors influencing the degradation process were studied by performing optimization experiments that resulted in rates of up to 0.008 L mg-1 min-1, more than twice as fast as using plasma gas treatment alone. These studies included mechanistic response of MCPD generated gaseous species with the IOP. In particular, reusability testing of IOP affirmed the robustness and performance efficiency up to three cycles. Finally, toxicity analysis revealed not only reduced negative effects on plant growth by the treated wastewater, but also it can used as minerals to plants. These findings highlight the feasibility of the IOP-MCPD system as a sustainable and eco-friendly solution to reduce scarcity of water in irrigation by treating textile effluent.
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The Zn element precipitates during aging in the Al-Zn binary alloy. Increased Zn content and prolonged aging leads to discontinuous Zn precipitation. The addition of 2 wt% Cu to the Al-43 wt%Zn alloy accelerates this discontinuous precipitation, resulting in decreased thickness of Zn layers and inter-distance between them. This acceleration is attributed to the influence of Cu solutes on the Zn phase, thereby reducing the interface energy between Zn precipitates and the Al matrix. The Al-Zn-Cu alloy demonstrates exceptional behavior during tensile tests, displaying a simultaneous increase in tensile strength and ductility alongside an 75 % reduction in area at room temperature drawing. Notably, despite the drawn beyond uniform deformation limit, there is an observed increase in total elongation. Our demonstration highlights this phenomenon, attributing it to the sustained coherent interface between the Zn layer and the Al matrix, as well as the uninterrupted continuity of Zn layers during drawing.
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This study presents a thorough investigation of the novel application of graphene oxide (GO) modified with melamine formaldehyde to fabricate granular three-dimensional GO (3D-GO), followed by the introduction of UiO-66 doping (3D-GO/U) for high uranium (U) adsorption. The U(VI) adsorption isotherms revealed that 3D-GO/U-10 with 10 % UiO-66 incorporation exhibited an impressive adsorption capacity of 375.5 mg g-1 and remained high U(VI) sorption performance in wide pH range. The introduction of UiO-66 to 3D-GO (3D-GO/U-10) led to the deagglomeration of the UiO-66 particles. The in situ surface-enhanced-Raman-spectroscopy-analysis and density-functional-theory simulations showed the symmetric metal center site Zr-O2 on UiO-66 was discovered to exhibit the highest adsorption energy (-3.21 eV) for U(VI) species due to the electrons transfer from the oxygen atom to U(VI) drives the covalent bonding between the symmetric metal center sites Zr-O2 and U(VI) on 3D-GO/U-10. The 3D-GO/U-10 was regenerated using a 0.1 M Na2CO3/0.01 M H2O2 solution and achieved up to 89.7 % U(VI) removal in the 5th cycle. The continuous flow column experiments results revealed 3D-GO/U-10 can regenerate and maintain a U(VI) removal capacity of â¼76 % for up to 4 cycles column experiments. Therefore, 3D-GO/U-10 exhibits great potential for removing U(VI) from water bodies.
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PURPOSE: This study aimed to analyze the latent class of suicide-related behaviors among Korean adolescents and identify related factors. METHODS: This study used 2021 Korean Youth Risk Behavior Web-Based Survey data and analyzed 7300 participants using latent class analysis. RESULTS: Suicide-related behaviors were categorized into four classes: suicide ideation only (Class 1), suicide plan without ideation or attempt (Class 2), suicide attempt with ideation and plan (Class 3), and suicide attempt without ideation or plan (Class 4). Sexual intercourse experience, habitual drug use experience, and hospital treatment experience due to violence, which were set as risky behavior-related variables, were found to be factors influencing Class 3. However, these variables were not statistically significant factors affecting those belonging to Class 2 and Class 4. CONCLUSION: The findings emphasize the necessity of understanding the variances in suicide-related behaviors among adolescents to tailor interventions effectively. Adolescents who plan and attempt suicide despite having low levels of suicidal ideation exhibited high levels of stress and a tendency for sadness and despair compared to the suicide attempt with the ideation and plan group. These insights underscore the importance of addressing psycho-emotional factors and developing intervention strategies that cater specifically to the nuanced needs of each group to prevent potential suicide attempts.
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Conducta del Adolescente , Análisis de Clases Latentes , Ideación Suicida , Intento de Suicidio , Humanos , Adolescente , Femenino , Masculino , República de Corea , Intento de Suicidio/estadística & datos numéricos , Intento de Suicidio/psicología , Conducta del Adolescente/psicología , Factores de Riesgo , Encuestas y Cuestionarios , Asunción de RiesgosRESUMEN
Motile cilia are crucial for maintaining healthy bodily functions by facilitating fluid transport and removing foreign substances or debris from the body. The dysfunction of motile cilia leads to ciliopathy. In particular, damage to the motile cilia of the airways can cause or worsen respiratory disease, making it an attractive target for therapeutic interventions. However, there are no treatments to induce motile ciliogenesis. Forkhead box transcription factor J1 (FOXJ1), the master regulator, has been implicated in motile cilia formation. Mice lacking the Foxj1 gene show loss of axoneme, a key component of cilia, that further highlights the importance of FOXJ1 in motile cilia formation. This prompted us to identify new small molecules that could induce motile ciliogenesis. A phenotype-based high-throughput screening (HTS) in a Tg(foxj1a:eGFP) zebrafish model was performed and a novel hit compound was identified. Among the synthesized compounds, compound 16c effectively enhanced motile ciliogenesis in a transgenic zebrafish model. To further test the efficacy of compound 16c on a mammalian airway system consisting of multiciliated cells (MCCs), ex vivo mice tracheal epithelial cell culture was adopted under an air-liquid interface system (ALI). Compound 16c significantly increased the number of MCCs by enhancing motile ciliogenesis. In addition, compound 16c exhibited good liver microsomal stability, in vivo PK profiles with AUC, and oral bioavailability. There was no significant inhibition of CYP and hERG, and no cell cytotoxicity was shown. In an elastase-induced COPD (chronic obstructive pulmonary disease) mouse model, compound 16c effectively prevented the development and onset of COPD. Taken together, compound 16c has great promise as a therapeutic agent for treating and alleviating motile ciliopathies.
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Cilios , Descubrimiento de Drogas , Piridinas , Pez Cebra , Animales , Cilios/efectos de los fármacos , Cilios/metabolismo , Ratones , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Humanos , Relación Estructura-Actividad , Estructura Molecular , Animales Modificados Genéticamente , Factores de Transcripción Forkhead/metabolismo , Relación Dosis-Respuesta a DrogaRESUMEN
The chiton (Polyplacophora) occupies a significant position in molluscan evolutionary history as one of the most primitive groups within the phylum Mollusca. Acanthochitona defilippii (Tapparone-Canefri 1874) (Chitonida: Acanthochitonidae) is a commonly found intertidal chiton species in South Korea. In this study, we characterized the complete mitochondrial genome of A. defilippii (14,999 bp long), comprising 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and an A + T rich region (166 bp). The base composition is as follows: 31.82% for A, 11.63% for C, 16.69% for G, and 39.86% for T. We reconstructed a maximum likelihood (ML) tree to elucidate phylogenetic relationships among the eight chitonid families using the nucleotide sequences of all PCGs. The ML tree revealed that A. defilippii clustered with Acanthochitona avicula (BP 100) within the family Acanthochitonidae. Acanthochitonidae formed a sister group with Mopaliidae. The results could provide a valuable understanding the phylogenetic relationships of chitonid species.
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Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd = 67 nM and onset of k = 0.136 min-1 (7.35 min) were determined. Serum stability was measured with a half-life of T1/2 = 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.
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HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor-associated macrophages (TAMs). Although TAMs consist of the immune-stimulatory M1 type and immune-suppressive M2 type, the M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1- versus M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2-TAMs convert arginine to polyamines (PAs). We hypothesize that such distinct arginine metabolism in M1- versus M2-TAMs is attributed to different availability of BH4 (NO synthase cofactor) and that its replenishment would reprogram M2-TAMs to M1-TAMs. Recently, we reported that sepiapterin (SEP), the endogenous BH4 precursor, elevates the expression of M1-TAM markers within HER2+ tumors. Here, we show that SEP restores BH4 levels in M2-like macrophages, which then redirects arginine metabolism to NO synthesis and converts M2 type to M1 type. The reprogrammed macrophages exhibit full-fledged capabilities of antigen presentation and induction of effector T cells to trigger immunogenic cell death of HER2+ cancer cells. This study substantiates the utility of SEP in the metabolic shift of the HER2+ breast tumor microenvironment as a novel immunotherapeutic strategy.
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Arginina , Neoplasias de la Mama , Óxido Nítrico , Microambiente Tumoral , Macrófagos Asociados a Tumores , Arginina/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Femenino , Humanos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Ratones , Microambiente Tumoral/inmunología , Animales , Óxido Nítrico/metabolismo , Reprogramación Celular , Línea Celular Tumoral , Macrófagos/metabolismo , Macrófagos/inmunologíaRESUMEN
Chronic obstructive pulmonary disease (COPD) and lung cancer represent formidable challenges in global health, characterized by intricate pathophysiological mechanisms and multifaceted disease progression. This comprehensive review integrates insights from diverse perspectives to elucidate the intricate roles of long non-coding RNAs (lncRNAs) in the pathogenesis of COPD and lung cancer, focusing on their diagnostic, prognostic, and therapeutic implications. In the context of COPD, dysregulated lncRNAs, such as NEAT1, TUG1, MALAT1, HOTAIR, and GAS5, emerge as pivotal regulators of genes involved in the disease pathogenesis and progression. Their identification, profiling, and correlation with the disease severity present promising avenues for prognostic and diagnostic applications, thereby shaping personalized disease interventions. These lncRNAs are also implicated in lung cancer, underscoring their multifaceted roles and therapeutic potential across both diseases. In the domain of lung cancer, lncRNAs play intricate modulatory roles in disease progression, offering avenues for innovative therapeutic approaches and prognostic indicators. LncRNA-mediated immune responses have been shown to drive lung cancer progression by modulating the tumor microenvironment, influencing immune cell infiltration, and altering cytokine production. Their dysregulation significantly contributes to tumor growth, metastasis, and chemo-resistance, thereby emphasizing their significance as therapeutic targets and prognostic markers. This review summarizes the transformative potential of lncRNA-based diagnostics and therapeutics for COPD and lung cancer, offering valuable insights into future research directions for clinical translation and therapeutic development.
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Progresión de la Enfermedad , Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Pronóstico , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genéticaRESUMEN
STUDY OBJECTIVE: To compare the effects of neostigmine/glycopyrrolate (a traditional agent) and sugammadex on bowel motility recovery and the occurrence of digestive system complications after colorectal surgery. DESIGN: Prospective, randomized controlled trial. SETTING: A single tertiary center. PATIENTS: 111 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: Patients were randomized into two groups based on the block reversal agent: 1) a mixture of 50 µg.kg-1 of neostigmine and 10 µg.kg-1 of glycopyrrolate (neostigmine group) and 2) 2 mg.kg-1 of sugammadex (sugammadex group). MEASUREMENTS: The primary outcome was the time from the surgery's completion to the first flatus. The time to the first postoperative defecation, incidences of postoperative nausea or vomiting, ileus, and dry mouth, as well as postoperative length of stay, were also assessed. MAIN RESULTS: The time to the first flatus was significantly shorter in the sugammadex group than in the neostigmine group (59 [42-79] h vs 69 [53-90] h, P = 0.027). The time to the first defecation and the incidences of postoperative nausea or vomiting and ileus did not differ between the groups, nor did the postoperative length of stay. However, the incidence of postoperative dry mouth was significantly lower in the sugammadex group than in the neostigmine group (7 patients [13%] vs 39 patients [71%], P < 0.001). CONCLUSIONS: The time to the first flatus was shorter using 2 mg.kg-1 sugammadex to reverse the neuromuscular block for laparoscopic colorectal surgery compared to reversal with conventional neostigmine/glycopyrrolate.