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There is growing evidence that the KDM5 family of histone demethylases plays a causal role in human cancer. However, few studies have been reported on the KDM5 family in endometrial carcinoma (EC). Moreover, it was found that there was some correlation between the KDM5 family and FOXO1 in EC. The current study was performed to explore the expressions of KDM5A, KDM5B, and FOXO1 in endometrioid adenocarcinoma detected by immunohistochemistry; paracancer endometrium, simple hyperplastic endometrium, and normal endometrium were used as control groups to explore the possible diagnostic value of KDM5A and KDM5B expression in endometrioid adenocarcinoma, with the aim of evaluating the potential of this marker in predicting the prognosis of endometrioid adenocarcinoma.
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Biomarcadores Tumorais , Carcinoma Endometrioide , Neoplasias do Endométrio , Proteína Forkhead Box O1 , Imuno-Histoquímica , Histona Desmetilases com o Domínio Jumonji , Humanos , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Feminino , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Histona Desmetilases com o Domínio Jumonji/metabolismo , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/metabolismo , Adulto , Idoso , Prognóstico , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Proteína 2 de Ligação ao Retinoblastoma/análise , Relevância Clínica , Proteínas Nucleares , Proteínas RepressorasRESUMO
Mast cells (MCs) are bone-marrow-derived haematopoietic cells that are widely distributed in human tissues. When activated, they will release tryptase, histamine and other mediators that play major roles in a diverse array of diseases/disorders, including allergies, inflammation, cardiovascular diseases, autoimmune diseases, cancers and even death. The multiple pathological effects of MCs have made their stabilizers a research hotspot for the treatment of related diseases. To date, the clinically available MC stabilizers are limited. Considering the rapidly increasing incidence rate and widespread prevalence of MC-related diseases, a comprehensive reference is needed for the clinicians or researchers to identify and choose efficacious MC stabilizers. This review analyzes the mechanism of MC activation, and summarizes the progress made so far in the development of MC stabilizers. MC stabilizers are classified by the action mechanism here, including acting on cell surface receptors, disturbing signal transduction pathways and interfering exocytosis systems. Particular emphasis is placed on the clinical applications and the future development direction of MC stabilizers.
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Mastócitos , Humanos , Mastócitos/imunologia , Mastócitos/metabolismo , Mastócitos/efeitos dos fármacos , Animais , Transdução de Sinais , Terapia de Alvo MolecularRESUMO
Background: Acute liver injury (ALI), which is a type of inflammation-mediated hepatocellular injury, is a clinical syndrome that results from hepatocellular apoptosis and hemorrhagic necrosis. Apoptosis stimulating protein of p53-2 (ASPP2) is a proapoptotic member of the p53 binding protein family. However, the role of ASPP2 in the pathogenesis of ALI and its regulatory mechanisms remain unclear. Methods: The expression of ASPP2 were compared between liver biopsies derived from patients with CHB, patients with ALI, and normal controls. Acute liver injury was modelled in mice by administration of D-GalN/LPS. Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. ASPP2-knockdown mice (ASPP2+/-) were used to determine its role in acute liver injury. Mouse bone marrow macrophages (BMMs) were isolated from wildtype and ASPP2+/- mice and stimulated with LPS, and the supernatant was collected to incubate with the primary hepatocytes. Quantitative real-time PCR and western blot were used to analyze the expression level of target. Results: The expression of ASPP2 was significantly upregulated in the liver tissue of ALI patients and acute liver injury mice. ASPP2+/- mice significantly relieved liver injury through reducing liver inflammation and decreasing hepatocyte apoptosis. Moreover, the conditioned medium (CM) of ASPP2+/- bone marrow-derived macrophages (BMMs) protected hepatocytes against apoptosis. Mechanistically, we revealed that ASPP2 deficiency in BMMs specifically upregulated IL-6 through autophagy activation, which decreased the level of TNF-α to reduce hepatocytes apoptosis. Furthermore, up-regulation of ASPP2 sensitizes hepatocytes to TNF-α-induced apoptosis. Conclusion: Our novel findings show the critical role of ASPP2 in inflammatory immunoregulatory mechanism of ALI and provide a rationale to target ASPP2 as a refined therapeutic strategy to ameliorate acute liver injury.
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Proteínas Reguladoras de Apoptose , Apoptose , Animais , Humanos , Camundongos , Masculino , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genética , Camundongos Knockout , Fígado/patologia , Fígado/metabolismo , Fígado/imunologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/metabolismo , Feminino , Lipopolissacarídeos , Pessoa de Meia-Idade , Macrófagos/imunologia , Macrófagos/metabolismo , Adulto , Proteínas Supressoras de TumorRESUMO
Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.
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Adaptação Fisiológica , Relógios Circadianos , Cyprinidae , Relógios Circadianos/genética , Cyprinidae/anatomia & histologia , Cyprinidae/genética , Cyprinidae/fisiologia , Cruzamento , Comportamento Sexual Animal/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Masculino , Feminino , Estações do Ano , Fígado/metabolismo , Baço , Rim , Proteínas de Peixes/genética , Expressão Gênica/fisiologiaRESUMO
The aim of this study was to determine whether the pretreatment CD8 + PD-1 + to CD4 + PD-1 + (PERLS) ratio is an independent risk prognostic factor of advanced melanoma patients. We retrospectively analyzed the efficacy and flow cytometry data from advanced melanoma patients who received PD-1 inhibitor as monotherapy between January 1, 2018 and January 26, 2022. Fifty-nine patients were enrolled, the PERLS cutoff was 1.125. PERLS did not correlate with clinical characteristics but were significantly associated with baseline CD8 + , CD4 + , and CD8 + PD-1 + T cells. The mean overall survival and the progression-free survival were 45.8 and 17.1â months for the low PERLS group (nâ =â 39), compared with 29.9 ( P â =â 0.001) and 9.7 ( P â =â 0.003) months for the high PERLS group ( n â =â 20), respectively. Pretreatment PERLS might contribute to selecting patients before receiving anti-PD-1 therapy.
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Inibidores de Checkpoint Imunológico , Melanoma , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Estudos Retrospectivos , Idoso , Adulto , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Idoso de 80 Anos ou mais , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
Currently, the relationship between serum uric acid (SUA) and bone mineral density (BMD) in men remains controversial. This study aims to investigate the relationship between SUA and lumbar spine BMD in American men using data from the National Health and Nutrition Examination Survey (NHANES). A total of 6254 male subjects aged 12-80 years (mean age 35.52 ± 14.84 years) in the NHANES from 2011 to 2020 were analyzed. SUA was measured by DxC using the timed endpoint method, and lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were used to explore the relationship between SUA and BMD by adjusting for age, race/Hispanic origin, drinking behavior, smoking behavior, physical activity, body mass index (BMI), poverty-to-income ratio (PIR), total protein, serum calcium, cholesterol, serum phosphorus, and blood urea nitrogen. After correcting for the above confounders, it was found that SUA was positively associated with lumbar spine BMD in the range of SUA < 5 mg/dL (ß = 0.006 95% CI 0.003-0.009, P < 0.001), and BMD of individuals in the highest quartile of SUA was 0.020 g/cm2 higher than those in the lowest quartile of SUA (ß = 0.020 95% CI 0.008-0.032, P = 0.003). This study showed that SUA was positively correlated with lumbar spine BMD in American men within a certain range. This gives clinicians some insight into how to monitor SUA levels to predict BMD levels during adolescence when bone is urgently needed for growth and development and during old age when bone loss is rapid.
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Densidade Óssea , Ácido Úrico , Adolescente , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Inquéritos Nutricionais , Absorciometria de Fóton , Osso e Ossos , Vértebras Lombares/diagnóstico por imagemRESUMO
BACKGROUND: This study is undertaken to establish the accuracy and reliability of OrthoCalc, a 3D application designed for the evaluation of maxillary positioning. METHODS: We registered target virtual planned models, maxillary models from pre-operative and post-operative CT scans, and post-operative intra-oral scans to a common reference system, allowing for digital evaluation. To assess rotational changes, we introduced a novel measurement method based on virtual cuboid models. Displacement errors were calculated based on proposed registration matrices. We also compared OrthoCalc to established commercial medical software as a benchmark. RESULTS: Statistical significance calculated showed no significant differences between OrthoCalc and commercial software. the biggest error of 0.04 degree in rotation change was found in the yaw. A maximum displacement change of 0.75 mm was found in the X direction. CONCLUSIONS: Our study validates OrthoCalc as a precise and reliable tool for assessing maxillary position changes with six degrees of freedom in orthognathic surgery, endorsing its clinical utility.
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Procedimentos Cirúrgicos Ortognáticos , Cirurgia Assistida por Computador , Procedimentos Cirúrgicos Ortognáticos/métodos , Maxila/diagnóstico por imagem , Reprodutibilidade dos Testes , Fluxo de Trabalho , Software , Imageamento Tridimensional/métodos , Cirurgia Assistida por Computador/métodosRESUMO
Tumor recurrence and wound microbial infection after tumor excision are serious threats to patients. Thus, the strategy to supply a sufficient and sustained release of cancer drugs and simultaneously engineer antibacterial properties and satisfactory mechanical strength is highly desired for tumor postsurgical treatment. Herein, A novel double-sensitive composite hydrogel embedded with tetrasulfide-bridged mesoporous silica (4S-MSNs) is developed. The incorporation of 4S-MSNs into oxidized dextran/chitosan hydrogel network, not only enhances the mechanical properties of hydrogels, but also can increase the specificity of drug with dual pH/redox sensitivity, thereby allowing more efficient and safer therapy. Besides, 4S-MSNs hydrogel preserves the favorable physicochemical properties of polysaccharide hydrogel, such as high hydrophilicity, satisfactory antibacterial activity, and excellent biocompatibility. Thus, the prepared 4S-MSNs hydrogel can be served as an efficient strategy for postsurgical bacterial infection and inhibition of tumor recurrence.
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Quitosana , Nanopartículas , Humanos , Quitosana/farmacologia , Quitosana/química , Hidrogéis/farmacologia , Hidrogéis/química , Dextranos/farmacologia , Dextranos/química , Dióxido de Silício/química , Recidiva Local de Neoplasia , Nanopartículas/química , Antibacterianos/farmacologiaRESUMO
INTRODUCTION: Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. METHODS: Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. RESULTS: The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3ß and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3ß and FoxO3a were upregulated. CONCLUSIONS: Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.
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Depressão , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Farmacologia em Rede , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêuticoRESUMO
Three rat sarcoma (RAS) gene isoforms, KRAS, NRAS, and HRAS, constitute the most mutated family of small GTPases in cancer. While the development of targeted immunotherapies has led to a substantial improvement in the overall survival of patients with non-KRAS-mutant cancer, patients with RAS-mutant cancers have an overall poorer prognosis owing to the high aggressiveness of RAS-mutant tumors. KRAS mutations are strongly implicated in lung, pancreatic, and colorectal cancers. However, RAS mutations exhibit diverse patterns of isoforms, substitutions, and positions in different types of cancers. Despite being considered "undruggable", recent advances in the use of allele-specific covalent inhibitors against the most common mutant form of RAS in non-small-cell lung cancer have led to the development of effective pharmacological interventions against RAS-mutant cancer. Sotorasib (AMG510) has been approved by the FDA as a second-line treatment for patients with KRAS-G12C mutant NSCLC who have received at least one prior systemic therapy. Other KRAS inhibitors are on the way to block KRAS-mutant cancers. In this review, we summarize the progress and promise of small-molecule inhibitors in clinical trials, including direct inhibitors of KRAS, pan-RAS inhibitors, inhibitors of RAS effector signaling, and immune checkpoint inhibitors or combinations with RAS inhibitors, to improve the prognosis of tumors with RAS mutations.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Alelos , Inibidores de Checkpoint Imunológico , ImunoterapiaRESUMO
For high-performance dual-photoelectrode assay, developing a pair of photoactive materials with well-matched band structure and the design of a powerful sensing strategy are highly desirable. Herein, the Zn-TBAPy pyrene-based MOF and BiVO4/Ti3C2 Schottky junction were employed as photocathode and photoanode to form an efficient dual-photoelectrode system. The integration of the cascaded hybridization chain reaction (HCR)/DNAzyme-assisted feedback amplification with DNA walker-mediated cycle amplification strategy realizes femtomolar HPV16 dual-photoelectrode bioassay. Through the activation of the HCR cascaded with the DNAzyme system in the presence of HPV16, plentiful HPV16 analogs are generated that leads to exponential positive feedback signal amplification. Meanwhile on the Zn-TBAPy photocathode, the NDNA hybridizes with the bipedal DNA walker followed by circular cleavage by Nb.BbvCI NEase, producing a dramatically enhanced PEC readout. The achieved ultralow detection limit of 0.57 fM and a wide linear range of 10-6 nM-103 nM showcase the excellent performance of the developed dual-photoelectrode system.
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Técnicas Biossensoriais , DNA Catalítico , DNA Catalítico/química , Papillomavirus Humano 16/genética , Retroalimentação , DNA/química , Limite de Detecção , Técnicas EletroquímicasRESUMO
As the size of the population aged 65 and older continues to grow, the incidence and mortality rates of Alzheimer's disease (AD) are increasing annually. Unfortunately, current treatments only treat symptoms temporarily and do not alter the patients' life expectancy or course of AD. Mesenchymal stem cells (MSCs) have shown a certain therapeutic potential in neurodegenerative diseases including AD due to their neuroinflammatory regulation and neuroprotective effects. However, the low survival and homing rates of MSCs after transplantation seriously affect their therapeutic effectiveness. Therefore, appropriate in vitro preconditioning is necessary to increase the survival and homing rates of MSCs to improve their effectiveness in treating AD. Here we summarize the therapeutic mechanisms of MSCs in AD and the chemical reagents used for the pretreatment of MSCs.
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Doença de Alzheimer , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Doença de Alzheimer/terapia , Condicionamento PsicológicoRESUMO
Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29 âeV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.
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The development of covalent organic framework (COF) sonosensitizers with intrinsic sonodynamic effects is highly desirable. However, such COFs are generally constructed using small-molecule photosensitizers. Herein, we report that the reticular chemistry-based synthesis of COFs from two inert monomers yields a COF-based sonosensitizer (TPE-NN) with inherent sonodynamic activity. Subsequently, a nanoscale COF TPE-NN is fabricated and embedded with copper (Cu)-coordinated sites to obtain TPE-NN-Cu. Results show that Cu coordination can enhance the sonodynamic effect of TPE-NN, whereas ultrasound (US) irradiation for sonodynamic therapy can augment the chemodynamic efficacy of TPE-NN-Cu. Consequently, TPE-NN-Cu upon US irradiation shows high-performance anticancer effects based on mutually reinforced sono-/chemo-nanodynamic therapy. This study reveals the backbone-originated sonodynamic activity of COFs and proposes a paradigm of intrinsic COF sonosensitizers for nanodynamic therapy.
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Síndrome de Cockayne , Estruturas Metalorgânicas , Neoplasias , Humanos , Estruturas Metalorgânicas/farmacologia , Neoplasias/tratamento farmacológico , Cobre/farmacologiaRESUMO
BACKGROUND: Following muscle injury, fibro-adipogenic progenitors (FAPs) are rapidly activated and undergo apoptosis at the resolution stage, which is required for proper muscle regeneration. When excessive FAPs remain, it contributes to fibrotic and fatty infiltration, impairing muscle recovery. Mechanisms controlling FAP apoptosis remain poorly defined. We hypothesized that AMP-activated protein kinase (AMPK) in FAPs mediates their apoptosis during the muscle regeneration. METHODS: To test, AMPKα1fl/fl PDGFRαCre mice were used to knock out AMPKα1 in FAPs. Following AMPKα1 knockout, the mice were injected with phosphate-buffered saline or glycerol to induce muscle injury. Tibialis anterior muscle and FAPs were collected at 3, 7 and 14 days post-injury (dpi) for further analysis. RESULTS: We found that AMPKα1 deletion in FAPs enhanced p65 translocation to the nuclei by 110% (n = 3; P < 0.01). AMPKα1 knockout group had a higher gene expression of MMP-9 (matrix metalloproteinase-9) by 470% (n = 3; P < 0.05) and protein level by 39% (n = 3; P < 0.05). Loss of AMPKα1 up-regulated the active TGF-ß1 (transforming growth factor-ß1) levels by 21% (n = 3; P < 0.05). TGF-ß promoted apoptotic resistance, because AMPKα1-deficient group had 36% lower cleaved Caspase 3 (cCAS3) content (n = 3; P < 0.05). Fibrotic differentiation of FAPs was promoted, with increased collagen protein level by 54% (n = 3; P < 0.05). Moreover, obesity decreased phosphorylation of AMPK by 54% (n = 3; P < 0.05), which decreased cCAS3 in FAPs by 44% (n = 3; P < 0.05) and elevated collagen accumulation (52%; n = 3; P < 0.05) during muscle regeneration. CONCLUSIONS: These data suggest that AMPK is a key mediator of FAPs apoptosis, and its inhibition due to obesity results in fibrosis of regenerated muscle.
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Proteínas Quinases Ativadas por AMP , Doenças Musculares , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/metabolismo , Fibrose , Colágeno/metabolismo , RegeneraçãoRESUMO
Background and objectives: Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for degradation. Autophagy plays a regulatory role in various hematologic malignancies, including acute myeloid leukemia (AML). However, there are few bibliometric studies on the role of autophagy in AML. The purpose of this study is to clarify the role of autophagy in acute myeloid leukemia through bibliometric analysis. Methods: The literature on autophagy and AML research from 2003 to 2023 was searched in Web of Science Core Collection, and bibliometric tools such as VOSviewer 1.6.18, Cite Space (6.1.R3), RStudio (R package bibliometrix), and Scimago Graphica were used to understand the current status and hotspots of autophagy and AML research. The study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and to predict future development trends in this field by drawing relevant visualization maps. Results: A total of 343 articles were obtained, published in 169 journals, written by 2,323 authors from 295 institutions in 43 countries. The journals with the most publications were Blood and Oncotarget. China had the most publications, and Chongqing Medical University and Sun Yat-sen University had the most publications. The author with the highest number of publications was Tschan, Mario P. The main types of research included clinical research, in vitro experiments, in vivo experiments, public database information, and reviews, and the forms of therapeutic effects mainly focused on genetic regulation, traditional Chinese medicine combination, autophagy inhibitors, and drug targets. The research hotspots of autophagy and AML in the past 17 years have focused on genetic regulation, autophagy inhibition, and targeted drugs. Chemotherapy resistance and mitochondrial autophagy will be the forefront of research. Conclusion: The gradual increase in the literature on autophagy and AML research and the decline after 2022 could be a result of authors focusing more on the type of research and the quality of the literature. The current research hotspots are mainly genetic regulation, autophagy inhibition, and autophagy-related targeted drugs. In future, autophagy will remain the focus of the AML field, with research trends likely to focus more on AML chemotherapy resistance and mitochondrial autophagy.
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Immune dysfunction has been implicated in the pathogenesis of schizophrenia (SZ). Despite previous studies showing a broad link between immune dysregulation and the central nervous system of SZ, the exact relationship has not been completely elucidated. With immune infiltration analysis as an entry point, this study aimed to explore the relationship between schizophrenia and the immune system in more detail from brain regions, immune cells, genes, and pathways. Here, we comprehensively analyzed the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) between SZ and control groups. Differentially expressed genes (DEGs) and functional enrichment analysis showed that three brain regions were closely related to the immune system. Compared with PFC and STR, there were 20 immune-related genes (IRGs) and 42 immune pathways in HPC. The results of immune infiltration analysis showed that the differential immune cells in HPC were effector memory T (Tem) cells. The correlation of immune-related DEGs (IDEGs) and immune cells further analysis showed that NPY, BLNK, OXTR, and FGF12, were moderately correlated with Tem cells. Functional pathway analysis indicated that these four genes might affect Tem by regulating the PI3K-AKT pathway and the neuroactive ligand-receptor interaction pathway. The receiver operating characteristic curve (ROC) analysis results indicated that these four genes had a high diagnostic ability (AUC=95.19%). Finally, the disease animal model was successfully replicated, and further validation was conducted using the real-time PCR and the western blot. These results showed that these gene expression changes were consistent with our previous expression profiling. In conclusion, our findings suggested that HPC in SZ may be more closely related to immune disorders and modulate immune function through Tem, PI3K-Akt pathway, and neuroactive ligand-binding receptor interactions. To the best of our knowledge, the Immucell AI tool has been applied for the first time to analyze immune infiltration in SZ, contributing to a better understanding of the role of immune dysfunction in SZ from a new perspective.
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Esquizofrenia , Animais , Hipocampo/metabolismo , Sistema Imunitário/metabolismo , Ligantes , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismoRESUMO
OBJECTIVES: Accurate contouring of the clinical target volume (CTV) is a key element of radiotherapy in cervical cancer. We validated a novel deep learning (DL)-based auto-segmentation algorithm for CTVs in cervical cancer called the three-channel adaptive auto-segmentation network (TCAS). METHODS: A total of 107 cases were collected and contoured by senior radiation oncologists (ROs). Each case consisted of the following: (1) contrast-enhanced CT scan for positioning, (2) the related CTV, (3) multiple plain CT scans during treatment and (4) the related CTV. After registration between (1) and (3) for the same patient, the aligned image and CTV were generated. Method 1 is rigid registration, method 2 is deformable registration, and the aligned CTV is seen as the result. Method 3 is rigid registration and TCAS, method 4 is deformable registration and TCAS, and the result is generated by a DL-based method. RESULTS: From the 107 cases, 15 pairs were selected as the test set. The dice similarity coefficient (DSC) of method 1 was 0.8155 ± 0.0368; the DSC of method 2 was 0.8277 ± 0.0315; the DSCs of method 3 and 4 were 0.8914 ± 0.0294 and 0.8921 ± 0.0231, respectively. The mean surface distance and Hausdorff distance of methods 3 and 4 were markedly better than those of method 1 and 2. CONCLUSIONS: The TCAS achieved comparable accuracy to the manual delineation performed by senior ROs and was significantly better than direct registration.