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1.
FASEB J ; 38(13): e23819, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38984942

RESUMO

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.


Assuntos
Histona Desacetilases , Fibrose Peritoneal , Animais , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/prevenção & controle , Fibrose Peritoneal/patologia , Camundongos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Peritônio/patologia , Peritônio/metabolismo
2.
Sci Rep ; 14(1): 13993, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886474

RESUMO

Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring.


Assuntos
Aprendizado de Máquina , Transtornos do Neurodesenvolvimento , Humanos , Feminino , Fatores de Risco , Masculino , Gravidez , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Adulto , República da Coreia/epidemiologia , Estudos Retrospectivos , Recém-Nascido , Pré-Escolar , Criança
4.
Yonsei Med J ; 65(7): 380-388, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38910300

RESUMO

PURPOSE: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. MATERIALS AND METHODS: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. RESULTS: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140-6.649, p=0.024; OR=2.986, 95% CI=1.451-6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064-4.617, p=0.034). CONCLUSION: Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD.


Assuntos
Doença de Crohn , Avaliação Nutricional , Complicações Pós-Operatórias , Humanos , Doença de Crohn/cirurgia , Feminino , Masculino , Adulto , Estudos Retrospectivos , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Adulto Jovem , Recidiva , Relevância Clínica
5.
Adv Healthc Mater ; : e2401159, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822543

RESUMO

As an alternative to tissue adhesives, photochemical tissue bonding is investigated for advanced wound healing. However, these techniques suffer from relatively slow wound healing with bleeding and bacterial infections. Here, the versatile attributes of afterglow luminescent particles (ALPs) embedded in dopamine-modified hyaluronic acid (HA-DOPA) patches for accelerated wound healing are presented. ALPs enhance the viscoelastic properties of the patches, and the photoluminescence and afterglow luminescence of ALPs maximize singlet oxygen generation and collagen fibrillogenesis for effective healing in the infected wounds. The patches are optimized to achieve the strong and rapid adhesion in the wound sites. In addition, the swelling and shrinking properties of adhesive patches contribute to a nonlinear behavior in the wound recovery, playing an important role as a strain-programmed patch. The protective patch prevents secondary infection and skin adhesion, and the patch seamlessly detaches during wound healing, enabling efficient residue clearance. In vitro, in vivo, and ex vivo model tests confirm the biocompatibility, antibacterial effect, hemostatic capability, and collagen restructuring for the accelerated wound healing. Taken together, this research collectively demonstrates the feasibility of HA-DOPA/ALP patches as a versatile and promoting solution for advanced accelerated wound healing, particularly in scenarios involving bleeding and bacterial infections.

6.
Cancer Res Commun ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916448

RESUMO

Immune checkpoint inhibitors are effective first-line therapy for solid cancers. However, low response rate and acquired resistance over time has led to the need for additional therapeutic options. Here, we evaluated synergistic anti-tumor efficacy of EGFR x MET targeting bispecific antibody, amivantamab with PD-L1 immunotherapy, pembrolizumab in head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) tumor bearing humanized PDX models. We demonstrated that pembrolizumab or amivantamab alone was ineffective and that combination treatment induced a significant reduction of tumor growth in both models (p<0.0001 and p<0.01, respectively). It appeared that combination of amivantamab and pembrolizumab significantly enhanced infiltration of granzyme B-producing CD8 T cells was in the TME of HNSCC PDX (p<0.01), and enhanced neoantigen-associated central memory CD8 T cells in circulating immune cells. Analysis of single cell RNA transcriptomics suggested that the tumor cells dramatically upregulated EGFR and MET in response to PD-L1 immunotherapy, potentially creating a metabolic state fit for tumor persistence in the tumor microenvironment (TME) and rendered pembrolizumab ineffective. We demonstrated that EGFRHIGHMETHIGH subcluster displayed an increased expression of genes implicated in production of lactate (SLC16A3 and LDHA) compared to the EGFRLOWMETLOW cluster. Accumulation of lactate in the TME has been associated with immunosuppression by hindering the infiltration of tumor killing CD8 T and NK cells. This study proved that amivantamab reduced glycolytic markers in the EGFRHIGHMETHIGH subcluster including SLC16A3 and LDHA and highlighted remodeling of the TME by combination treatment, providing rationale for additional therapy of amivantamab with PD-1 immunotherapy.

7.
Biol Res ; 57(1): 25, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720397

RESUMO

PURPOSE: Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. METHODS: PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. RESULTS: In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. CONCLUSION: Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.


Assuntos
Autofagia , Transição Epitelial-Mesenquimal , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Autofagia/fisiologia , Autofagia/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Inativação Gênica , Camundongos Nus , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
8.
J Microbiol Biotechnol ; 34(6): 1340-1347, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38783718

RESUMO

Ehretia asperula is a medicinal plant of the Ehretiaceae family used to treat inflammatory disorders, but the underlying mechanisms are not fully elucidated. The anti-inflammatory potential was determined based on enzyme cyclooxygenase-2 (COX-2) inhibition, which showed that the 95% ethanol extract (95ECH) was most effective with a half-maximal inhibitory concentration (IC50) value of 34.09 µg/mL. The effects of 95ECH on phagocytosis, NO production, gene, and protein expression of the cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) and inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathways in lipopolysaccharide (LPS)-induced RAW264.7 cells were examined using the neutral red uptake and Griess assays, reverse-transcriptase polymerase chain reactions (RTPCR), and enzyme-linked immunosorbent assays (ELISA). The results showed that 95ECH suppressed phagocytosis and the NO production in activated macrophage cells (p < 0.01). Conversely, 95ECH regulated the expression levels of mRNAs for cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) as well as the corresponding proteins. In addition, PGE2 production was inhibited in a dose-dependent manner by 95ECH, and the expression of iNOS and COX-2 mRNAs was decreased in activated macrophage cells, as expected. Therefore, 95ECH from E. asperula leaves contains potentially valuable compounds for use in inflammation management.


Assuntos
Anti-Inflamatórios , Ciclo-Oxigenase 2 , Dinoprostona , Lipopolissacarídeos , Macrófagos , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Fagocitose , Extratos Vegetais , Animais , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fagocitose/efeitos dos fármacos , Óxido Nítrico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Dinoprostona/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Citocinas/metabolismo , Interleucina-6/metabolismo , Interleucina-6/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética
9.
Food Funct ; 15(13): 7224-7237, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38812412

RESUMO

Yak-Kong (YK) is a small black soybean widely cultivated in Korea. It is considered to have excellent health functionality, as it has been reported to have better antioxidant efficacy than conventional black or yellow soybeans. Since YK has been described as good for the muscle health of the elderly in old oriental medicine books, this study sought to investigate the effect of fermented YK with Bifidobacterium animalis subsp. lactis LDTM 8102 (FYK) on muscle atrophy. In C2C12 mouse myoblasts, FYK elevated the expression of MyoD, total MHC, phosphorylated AKT, and PGC1α. In addition, two kinds of in vivo studies were conducted using both an induced and normal aging mouse model. The behavioral test results showed that in the induced aging mouse model, FYK intake alleviated age-related muscle weakness and loss of exercise performance. In addition, FYK alleviated muscle mass decrease and improved the expression of biomarkers including total MHC, myf6, phosphorylated AKT, PGC1α, and Tfam, which are related to myoblast differentiation, muscle protein synthesis, and mitochondrial generation in the muscle. In the normal aging model, FYK consumption did not increase muscle mass, but did upregulate the expression levels of biomarkers related to myoblast differentiation, muscle hypertrophy, and muscle function. Furthermore, it mitigated age-related declines in skeletal muscle force production and functional limitation by enhancing exercise performance and grip strength. Taken together, the results suggest that FYK has the potential to be a new functional food material that can alleviate the loss of muscle mass and strength caused by aging and prevent sarcopenia.


Assuntos
Envelhecimento , Bifidobacterium animalis , Atrofia Muscular , Animais , Camundongos , Atrofia Muscular/metabolismo , Masculino , Bifidobacterium animalis/fisiologia , Fermentação , Modelos Animais de Doenças , República da Coreia , Músculo Esquelético/metabolismo , Probióticos , Intestinos/microbiologia , Alimentos de Soja , Humanos , Mioblastos/metabolismo , Glycine max/química , Camundongos Endogâmicos C57BL
10.
Int J Stem Cells ; 17(2): 158-181, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38777830

RESUMO

This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.

11.
Neural Netw ; 176: 106362, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38733795

RESUMO

Appropriate weight initialization settings, along with the ReLU activation function, have become cornerstones of modern deep learning, enabling the training and deployment of highly effective and efficient neural network models across diverse areas of artificial intelligence. The problem of "dying ReLU," where ReLU neurons become inactive and yield zero output, presents a significant challenge in the training of deep neural networks with ReLU activation function. Theoretical research and various methods have been introduced to address the problem. However, even with these methods and research, training remains challenging for extremely deep and narrow feedforward networks with ReLU activation function. In this paper, we propose a novel weight initialization method to address this issue. We establish several properties of our initial weight matrix and demonstrate how these properties enable the effective propagation of signal vectors. Through a series of experiments and comparisons with existing methods, we demonstrate the effectiveness of the novel initialization method.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Algoritmos , Inteligência Artificial , Neurônios/fisiologia , Humanos
12.
Small ; : e2400638, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804126

RESUMO

The lithium deposited via the complex electrochemical heterogeneous lithium deposition reaction (LDR) process on a lithium foil-based anode (LFA) forms a high-aspect-ratio shape whenever the reaction kinetics reach its limit, threatening battery safety. Thereby, a research strategy that boosts the LDR kinetics is needed to construct a high-power and safe lithium metal anode. In this study, the kinetic limitations of the LDR process on LFA are elucidated through operando and ex situ observations using in-depth electrochemical analyses. In addition, ultra-thin (≈0.5 µm) and high modulus (≥19 GPa) double-walled carbon nanotube (DWNT) membranes with different surface properties are designed to catalyze high-safety LDRs. The oxygen-functionalized DWNT membranes introduced on the LFA top surface simultaneously induce multitudinous lithium nuclei, leading to film-like lithium deposition even at a high current density of 20 mA cm-2. More importantly, the layer-by-layer assembly of the oxygen-functionalized and pristine DWNT membranes results in different surface energies between the top and bottom surfaces, enabling selective surface LDRs underneath the high-modulus bilayer membranes. The protective LDR on the bilayer-covered LFA guarantees an invulnerable cycling process in large-area pouch cells at high current densities for more than 1000 cycles, demonstrating the practicability of LFA in a conventional liquid electrolyte system.

13.
Chaos ; 34(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717397

RESUMO

The metapopulation network model is a mathematical framework used to study the spatial spread of epidemics with individuals' mobility. In this paper, we develop a time-varying network model in which the activity of a population is correlated with its attractiveness in mobility. By studying the spreading dynamics of the SIR (susceptible-infectious-recovered)-type disease in different correlated networks based on the proposed model, we theoretically derive the mobility threshold and numerically observe that increasing the correction between activity and attractiveness results in a reduced mobility threshold but suppresses the fraction of infected subpopulations. It also introduces greater heterogeneity in the spatial distribution of infected individuals. Additionally, we investigate the impact of nonpharmaceutical interventions on the spread of epidemics in different correlation networks. Our results show that the simultaneous implementation of self-isolation and self-protection is more effective in negatively correlated networks than that in positively correlated or non-correlated networks. Both self-isolation and self-protection strategies enhance the mobility threshold and, thus, slow down the spread of the epidemic. However, the effectiveness of each strategy in reducing the fraction of infected subpopulations varies in different correlated networks. Self-protection is more effective in positively correlated networks, whereas self-isolation is more effective in negatively correlated networks. Our study will provide insights into epidemic prevention and control in large-scale time-varying metapopulation networks.


Assuntos
Epidemias , Humanos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/transmissão , Fatores de Tempo , Dinâmica Populacional
14.
Sci Rep ; 14(1): 9416, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658570

RESUMO

Rice (Oryza sativa L.) is an important member of the family Poaceae and more than half of world population depend for their dietary nutrition on rice. Rice cultivars with higher yield, resilience to stress and wider adaptability are essential to ensure production stability and food security. The fundamental objective of this study was to identify higher-yielding rice genotypes with stable performance and wider adaptability in a rice growing areas of Pakistan. A triplicate RCBD design experiment with 20 Green Super Rice (GSR) advanced lines was conducted at 12 rice growing ecologies in four Provinces of Pakistan. Grain yield stability performance was assessed by using different univariate and multivariate statistics. Analysis of variance revealed significant differences among genotypes, locations, and G x E interaction for mean squares (p < 0.05) of major yield contributing traits. All the studied traits except for number of tillers per plant revealed higher genotypic variance than environmental variance. Broad sense heritability was estimated in the range of 44.36% to 98.60%. Based on ASV, ASI, bi, Wi2, σ2i and WAAS statistics, the genotypes G1, G4, G5, G8, G11 and G12 revealed lowest values for parametric statistics and considered more stable genotypes based on  paddy yield. The additive main effects and multiplicative interaction (AMMI) model revealed significant variation (p < 0.05) for genotypes, non-signification for environment and highly significant for G × E interaction. The variation proportion of PC1 and PC2 from interaction revealed 67.2% variability for paddy yield. Based on 'mean verses stability analysis of GGE biplot', 'Which-won-where' GGE Biplot, 'discriminativeness vs. representativeness' pattern of stability, 'IPCA and WAASB/GY' ratio-based stability Heat-map, and ranking of genotypes, the genotypes G1, G2, G3, G5, G8, G10, G11 and G13 were observed ideal genotypes with yield potential more than 8 tons ha-1. Discriminativeness vs. representativeness' pattern of stability identifies two environments, E5 (D.I Khan, KPK) and E6 (Usta Muhammad, Baluchistan) were best suited for evaluating genotypic yield performance. Based on these findings we have concluded that the genotypes G1, G2, G3, G5, G8, G10, G11 and G13 could be included in the commercial varietal development process and future breeding program.


Assuntos
Genótipo , Oryza , Oryza/genética , Oryza/crescimento & desenvolvimento , Paquistão , Fenótipo , Melhoramento Vegetal/métodos , Interação Gene-Ambiente , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Característica Quantitativa Herdável
15.
Adv Sci (Weinh) ; 11(25): e2400460, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38654622

RESUMO

Lightweight structural materials are commonly used as effective fillers for advanced composites with high toughness. This study focused on enhancing the toughness of direct-spun carbon nanotube yarns (CNTYs) by controlling the micro-textural structure using a water-gap-based direct spinning. Drawing inspiration from the structural features of natural spider silk fibroin, characterized by an α-helix in the amorphous region and ß-sheet in the crystalline region, multiscale bundles within CNTYs are reorganized into a unique nano-coil-like structure. This nano-coiled structure facilitated the efficient dissipation of external mechanical loads through densification with the rearrangement of multiscale bundles, improving specific strength and strain. The resulting CNTYs exhibited exceptional mechanical properties with toughness reaching 250 J g-1, making them promising alternatives to commercially available fibers in lightweight, high-toughness applications. These findings highlight the significance of nano-coiling engineering for emulating bio-inspired micro-textural structures, achieving remarkable enhancement in the toughness of CNTYs.

16.
Front Immunol ; 15: 1330228, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680496

RESUMO

Introduction: Aryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers. Methods: Here, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression. Results: Our findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC). Discussion: These findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies.


Assuntos
Neoplasias , Receptores de Hidrocarboneto Arílico , Microambiente Tumoral , Receptores de Hidrocarboneto Arílico/metabolismo , Humanos , Microambiente Tumoral/imunologia , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Biomarcadores Tumorais/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
17.
Toxins (Basel) ; 16(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38668622

RESUMO

Post-stroke spasticity is a common complication that limits the functional performance of patients. Botulinum toxin (BTx) is an effective treatment for spasticity. Numerous researchers have applied extracorporeal shock wave therapy (ESWT) to address post-stroke spasticity, yielding positive clinical outcomes. We aimed to clarify the add-on effects of ESWT on BTx therapy for spasticity in patients with post-stroke. Sixteen eligible patients with upper extremity spasticity after stroke were recruited for this study. They were randomized to either a BTx with focused ESWT treatment group or a BTx alone group. Spasticity, measured using the modified Ashworth score (MAS) and modified Tardieu scale (MTS), showed statistically significant improvements in the elbow and wrist flexor muscles in both BTx + ESWT group and BTx alone groups. However, no significant differences were observed between the two groups with time flow. The BTx + ESWT group showed significantly decreased MAS of the finger flexors at follow-up and increased R1 (MTS) of the finger flexors at 3 weeks after treatment, which was not observed in the BTx alone group. This is the first study to identify the add-on effect of ESWT on BTx injections to improve post-stroke upper limb spasticity.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Espasticidade Muscular , Acidente Vascular Cerebral , Extremidade Superior , Humanos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Espasticidade Muscular/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Idoso , Resultado do Tratamento , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/administração & dosagem , Terapia Combinada , Adulto
18.
Ear Nose Throat J ; : 1455613241234818, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424695

RESUMO

Objective: To analyze changes in olfactory function after endoscopic endonasal skull base surgery and compare performance of the olfactory questionnaire with those of conventional psychophysical tests. Methods: Patients were classified into 5 categories for olfactory function evaluation (normal, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia) based on a self-assessment. Patients also underwent the butanol threshold test (BTT), Cross-Cultural Smell Identification Test (CCSIT), and 11-item olfactory questionnaire. Subjects with normosmia preoperatively and who were followed up at least 6 months after surgery were analyzed. Receiver operating characteristic curves and confusion matrix analysis were performed for BTT, CCSIT, and olfactory questionnaire to compare their diagnostic abilities. The effects of age, preoperative olfaction, septal flap, tumor pathology, and tumor size on postoperative olfaction were evaluated using multivariate linear regression analysis. Results: Data from 108 patients were analyzed. Postoperative changes in the olfactory questionnaire were significantly associated with changes in the BTT and CCSIT. The area under the curve for postoperative self-olfactory function classification was highest for olfactory questionnaire (0.894), followed by BTT (0.767) and CCSIT (0.688). Patient age at the time of surgery and preoperative BTT score were significantly related to postoperative olfactory outcomes. Conclusion: The olfactory questionnaire correlated well with conventional psychosomatic olfactory function tests. In combination with clinical parameters and preoperative psychosomatic olfactory function tests, the olfactory questionnaire is suitable for assessing subjective olfactory function after endoscopic endonasal skull base surgery.

19.
ACS Omega ; 9(8): 8632-8653, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38434807

RESUMO

Agriculture waste has increased annually due to the global food demand and intensive animal production. Preventing environmental degradation requires fast and effective agricultural waste treatment. Aerobic digestion or composting uses agricultural wastes to create a stabilized and sterilized organic fertilizer and reduces chemical fertilizer input. Indeed, conventional composting technology requires a large surface area, a long fermentation period, significant malodorous emissions, inferior product quality, and little demand for poor end results. Conventional composting loses a lot of organic nitrogen and carbon. Thus, this comprehensive research examined sustainable and adaptable methods for improving agricultural waste composting efficiency. This review summarizes composting processes and examines how compost additives affect organic solid waste composting and product quality. Our findings indicate that additives have an impact on the composting process by influencing variables including temperature, pH, and moisture. Compost additive amendment could dramatically reduce gas emissions and mineral ion mobility. Composting additives can (1) improve the physicochemical composition of the compost mixture, (2) accelerate organic material disintegration and increase microbial activity, (3) reduce greenhouse gas (GHG) and ammonia (NH3) emissions to reduce nitrogen (N) losses, and (4) retain compost nutrients to increase soil nutrient content, maturity, and phytotoxicity. This essay concluded with a brief summary of compost maturity, which is essential before using it as an organic fertilizer. This work will add to agricultural waste composting technology literature. To increase the sustainability of agricultural waste resource utilization, composting strategies must be locally optimized and involve the created amendments in a circular economy.

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