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BACKGROUND: Ionocytes are rare cells in airway epithelium characterized by a high expression of CFTR. OBJECTIVES: To investigate the morphology and distribution of ionocytes and the function of CFTR in the nasal mucosal epithelium of children. METHODS: The exfoliated cells of nasal mucosa from 101 children were detected using flow cytometry to analyze the number of ionocytes and CFTR and the difference of CFTR function. Nasal mucosa and polyps were collected from 10 children with CRSwNP. The RNAscope of FOXI1 and CFTR was detected in pathological paraffin sections. The expression and distribution of ionocytes and CFTR in nasal mucosa and polyp epithelium were observed. RESULTS: In CRS patients, the number of ionocytes in the nasal epithelium was lower and the number of ionocytes that did not express CFTR was higher, and the function of CFTR was also decreased. The expression of CFTR in the nasal mucosa of CRS showed the characteristics of local dense distribution and increased as the inflammation expanded. The ionocytes were "tadpole-shaped" in the epithelium and gathered in the area of high CFTR expression, the intracellular CFTR was expanded in clusters. Ionocytes that did not express CFTR was more common in the nasal polyps. CONCLUSIONS: The number of ionocytes and the function of CFTR in nasal mucosa of CRS patients decreased. With the expansion of inflammation, CFTR and ionocytes showed more obvious dense distribution. Some ionocytes lost the expression of CFTR and did not show the "tadpole" shape, which may be related to the occurrence of polyps.
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Pólipos Nasais , Rinite , Sinusite , Humanos , Criança , Rinite/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Sinusite/patologia , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Inflamação/patologia , Doença Crônica , Fatores de Transcrição ForkheadRESUMO
High levels of M2 macrophage infiltration invariably contribute to poor cancer prognosis and can be manipulated by metabolic reprogramming in the tumor microenvironment. However, the metabolism-related genes (MRGs) affecting M2 macrophage infiltration and their clinical implications are not fully understood. In this study, we identified 173 MRGs associated with M2 macrophage infiltration in cases of gastric cancer (GC) using the TCGA and GEO databases. Twelve MRGs were eventually adopted as the prognostic signature to develop a risk model. In the high-risk group, the patients showed poorer survival outcomes than patients in the low-risk group. Additionally, the patients in the high-risk group were less sensitive to certain drugs, such as 5-Fluorouracil, Oxaliplatin, and Cisplatin. Risk scores were positively correlated with the infiltration of multiple immune cells, including CD8+ T cells and M2 macrophages. Furthermore, a difference was observed in the expression and distribution between the 12 signature genes in the tumor microenvironment through single-cell sequencing analysis. In vitro experiments proved that the M2 polarization of macrophages was suppressed by Sorcin-knockdown GC cells, thereby hindering the proliferation and migration of GC cells. These findings provide a valuable prognostic signature for evaluating clinical outcomes and corresponding treatment options and identifying potential targets for GC treatment.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Prognóstico , Cisplatino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Macrófagos , Microambiente Tumoral/genéticaRESUMO
Allergic rhinitis(AR) is a common chronic inflammatory disease of the upper respiratory tract. Due to its high prevalence, high recurrence rate, and lack of a definitive cure, it is considered a global health issue by the World Health Organization. The pathogenesis of AR is complex and mainly involves B cells, helper T cells, eosinophils, basophils, macrophages, as well as the cytokines and inflammatory mediators they secrete. Clinical treatment primarily focuses on inhibiting inflammatory mediators such as histamine and leukotrienes. In recent years, active ingredients of animal-derived traditional Chinese medicine(TCM) have shown unique advantages and potential in AR treatment thanks to their high safety, specificity, selectivity, and biopotency. This study systematically reviewed the therapeutic effects and mechanisms of active ingredients and mixed extracts from animal-derived TCM, such as bovine spleen, honeycomb, bee venom, maggot, and human placenta, which have been shown by modern pharmacological research to regulate the immune function in AR, providing a reference for further exploration and clinical development of active ingredients from animal-derived TCM. Studies have found that the active ingredients from animal-derived TCM can produce definite therapeutic effects in AR by modulating multiple immune balances in the body, with great clinical prospects. However, their mechanisms of action still require further investigation, and the quality control techniques for effective ingredients need to be improved. Currently, the research on active ingredients from animal-derived TCM in China has adopted an interactive system consisting of "traditional medical experience-based research, bioinformatics and artificial intelligence predictions, and validation and development through new experimental techniques". Based on this system, animal-derived TCM can combine modern scientific and technological means to maximize the therapeutic effects of active ingredients and serve the clinical application of AR in a more efficient and innovative manner.
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Medicamentos de Ervas Chinesas , Poríferos , Rinite Alérgica , Animais , Bovinos , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inteligência Artificial , Rinite Alérgica/tratamento farmacológico , Mediadores da InflamaçãoRESUMO
The intestinal tract is an essential component of the body's immune system, and is extremely sensitive to exposure of ionizing radiation. While ionizing radiation can effectively induce multiple forms of cell death, whether it can also promote ferroptosis in intestinal cells and the possible interrelationship between ferroptosis and intestinal immune function has not been reported so far. Here, we found that radiation-induced major ultrastructural changes in mitochondria of small intestinal epithelial cells and the changes induced in iron content and MDA levels in the small intestine were consistent with that observed during cellular ferroptosis, thus suggesting occurrence of ferroptosis in radiation-induced intestinal damage. Moreover, radiation caused a substantial increase in the expression of ferroptosis-related factors such as LPCAT3 and ALOX15 mRNA, augmented the levels of immune-related factors INF-γ and TGF-ß mRNA, and decreased the levels of IL-17 mRNA thereby indicating that ionizing radiation induced ferroptosis and impairment of intestinal immune function. Liproxstatin-1 is a ferroptosis inhibitor that was found to ameliorate radiation-induced ferroptosis and promote the recovery from immune imbalances. These findings supported the role of ferroptosis in radiation-induced intestinal immune injury and provide novel strategies for protection against radiation injury through regulation of the ferroptosis pathway.
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Ferroptose/fisiologia , Intestinos/patologia , Quinoxalinas/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Radiação Ionizante , Compostos de Espiro/farmacologia , 1-Acilglicerofosfocolina O-Aciltransferase/genética , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , Animais , Araquidonato 12-Lipoxigenase/genética , Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/metabolismo , Ferroptose/efeitos dos fármacos , Ferroptose/efeitos da radiação , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Glutationa/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/efeitos da radiação , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Mitocôndrias/ultraestrutura , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/fisiopatologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major health issues worldwide. Pathophysiological changes in COPD are mainly reflected in the deterioration of lung function with aging. METHODS: Considering that telomere length is a hallmark of biological aging, we first performed a meta-analysis to summarize the current knowledge about the relationship between telomere length and COPD and then employed individual-level data from the continuous National Health and Nutrition Examination Survey (NHANES) to investigate whether telomere length could reflect accelerated aging in COPD and serve as an independent predictor. A mediation study was further performed to examine whether the association between telomeres and COPD could be mediated by inflammation, as one of the most important etiologies and characteristics of COPD. RESULTS: The four studies included in our meta-analysis were with high heterogeneity (I2 = 95.7%, Phet < 0.001), and the pooled relative risk for COPD comparing the shortest tertile versus the longest tertile was 4.06 (95% CI = 1.38 to 11.96). Of the 6,378 subjects in the individual-level data analyses using NHANES, 455 were diagnosed with COPD, and multivariable-adjusted logistic regression also indicated that short telomere length was associated with COPD. Consistently, cubic regression spline analyses showed that long telomeres exhibited a significant association with a decreased risk of COPD. In the subsequent mediation analyses, C-reactive protein concentration, white blood cells count and blood neutrophil count, as inflammatory biomarkers, showed a significant indirect effect on the relationship between telomere length and COPD. CONCLUSION: Accelerated aging in COPD could be characterized by excessive telomere shortening, and inflammatory response might be involved in the underlying mechanisms of COPD pathogenesis promoted by short telomere length. Telomere length measurement may facilitate clinical translational research and targeted therapy of COPD.
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Doença Pulmonar Obstrutiva Crônica , Fumar , Envelhecimento , Humanos , Inflamação/genética , Leucócitos , Inquéritos Nutricionais , TelômeroRESUMO
As the greatest medical and socioeconomic problem in developing countries, stroke is the second or third leading cause of death in China and worldwide. In adult organisms suffering from stroke, transplanted stem cells have the ability to repair damaged tissues by regenerating autologous cells, while ginsenoside Rg1 could promote proliferation and differentiation of stem cells. Although obvious antistroke effects of ginsenoside Rg1 and transplanted stem cells have been verified in publications, the mechanism exploration remains challenging. Our study was carried out to investigate the synergistic effects of ginsenoside Rg1 and neural stem cell (NSC) transplantation on MCAO rats with a 1H NMR-based nontargeted metabolomics method to identify potential biomarkers and protein targets and discover the potential mechanism. NSCs transplantation after MCAO combined with ginsenoside Rg1 administration could significantly improve the cerebral infarct and neurological deficits. The treatment significantly intervened the levels of ten metabolites, and perturbed energy metabolism, amino acids metabolism, and lipids metabolism. And 11 enzymes were identified and verified as the targets of NSCs transplantation and ginsenoside Rg1 administration on MCAO rats. Our findings helped to improve the antistroke mechanism of NSCs transplantation and ginsenoside Rg1 and supply a theory basis for the combined research of stem cells and Chinese medicine in the future.
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Isquemia Encefálica , Ginsenosídeos , AVC Isquêmico , Células-Tronco Neurais , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/tratamento farmacológico , China , Ginsenosídeos/farmacologia , Metabolômica , Ratos , Transplante de Células-Tronco , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Type 2 diabetes mellitus is the most common type of diabetes, and insulin resistance (IR) is its core pathological mechanism. Proteomics is an ingenious and promising Omics technology that can comprehensively describe the global protein expression profiling of body or specific tissue, and is widely applied to the study of molecular mechanisms of diseases. In this paper, we focused on insulin target organs: adipose tissue, liver, and skeletal muscle, and analyzed the different pathological processes of IR in these three tissues based on proteomics research. By literature studies, we proposed that the main pathological processes of IR among target organs were diverse, which showed unique characteristics and focuses. We further summarized the differential proteins in target organs which were verified to be related to IR, and discussed the proteins that may play key roles in the emphasized pathological processes, aiming at discovering potentially specific differential proteins of IR, and providing new ideas for pathological mechanism research of IR.
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Tecido Adiposo/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Músculo Esquelético/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/metabolismo , Proteômica/métodosRESUMO
Allergic rhinitis (AR) negatively affects the healthy lives of many individuals. Most previous studies on AR focused on the expression of cytokines, with only a few analyzing cytokine expression from a metabolomics viewpoint. Therefore, it is worthwhile to study AR at the metabolic level. Consequently, we aimed to identify differential serum biomarkers by metabolomics. In this study, the orthogonal partial least squares discriminant analysis (OPLS-DA) model was applied to characterize the differences in serum samples collected from patients with AR and healthy volunteers. Ten metabolites (except hexadecanoic acid) were found to be altered significantly (p < .05) in the former group, according to results of principal component analysis and OPLS-DA, indicating that these metabolites could be potential biomarkers. MetaboAnalyst 4.0 and pathway enrichment analysis showed that these changes in metabolites mainly involved three pathways, namely, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and purine metabolism. Our findings may contribute to a better understanding of the potential pathogenesis mechanisms and provide a metabolic evidence for in-depth studies of AR.
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Metaboloma/fisiologia , Metabolômica/métodos , Rinite Alérgica/sangue , Rinite Alérgica/metabolismo , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-IdadeRESUMO
Microorganisms play a significant role in uranium(VI) biogeochemistry and influence U(VI) transformation through biomineralization. In the present work, the process of uranium mineralization was investigated by Saccharomyces cerevisiae. The toxicity experiments showed that the viability of cell was not significantly affected by 100 mg L-1 U(VI) under 4 days of exposure time. The batch experiments showed that the phosphate concentration and pH value increased over time during U(VI) adsorption. Meanwhile, thermodynamic calculations demonstrated that the adsorption system was supersaturated with respect to UO2HPO4. The X-ray powder diffraction spectroscopy (XRD), field emission scanning electron microscopy (FE-SEM) equipped with energy dispersive spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analyses indicated that the U(VI) was first attached onto the cell surface and reacted with hydroxyl, carboxyl, and phosphate groups through electrostatic interactions and complexation. As the immobilization of U(VI) transformed it from the ionic to the amorphous state, lamellar uranium precipitate was formed on the cell surface. With the prolongation of time, the amorphous uranium compound disappeared, and there were some crystalline substances observed extracellularly, which were well-characterized as tetragonal-chernikovite. Furthermore, the size of chernikovite was regulated at nano-level by cells, and the perfect crystal was formed finally. These findings provided an understanding of the non-reductive transformation process of U(VI) from the amorphous to crystalline state within microbe systems, which would be beneficial for the U(VI) treatment and reuse of nuclides and heavy metals.
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Microbiologia Industrial , Saccharomyces cerevisiae/metabolismo , Urânio/química , Urânio/metabolismo , Adsorção , Microscopia Eletrônica de Varredura , Fosfatos/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Urânio/toxicidadeRESUMO
A drug's physical characteristics, such as colour, could be factors influencing its therapeutic effects. It is not well understood whether people's expectations on drug effects and efficacy are affected by colour, especially among Chinese population. This study was conducted to examine people's expectations on drug effects and efficacy on the basis of drug colour, and to reveal possible gender differences in colour-related drug expectations. Participants (n = 224) were asked to classify seven single-coloured and six two-coloured capsules into one of four categories of drug effects, and to indicate the strength of drug efficacy. It is found that all the coloured capsules yielded non-chance distributions in classifications of drug effects, with six single-coloured and four two-coloured capsules associated with specific drug effects. Colour also conveyed differential strengths of drug efficacy in general and in relation to specific drug effects. There were gender differences in drug expectations for some colours and colour combinations. Practitioner Summary: Drug colour was found to have impacts on perceived drug effects and efficacy. The findings from the present study can be used by ergonomics practitioners to design appropriate drug colours in support of drug differentiation, therapeutic effects and medication adherence.
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Cor , Percepção , Preparações Farmacêuticas , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas/classificação , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
Mechanical properties such as hardness and modulus of sodium borosilicate (NBS) glasses in irradiation conditions were studied extensively in recent years. With irradiation of heavy ions, a trend that the hardness of NBS glasses decreased and then stabilized with increase of dose has been reported. Variations in network structures were suggested for the decrease of hardness after irradiation. However, details of these variations in a network of glass are not clear yet. In this paper, molecular dynamics was applied to simulate the network variations in a type of NBS glass and the changes in hardness after xenon irradiation. The simulation results indicated that hardness variation decreased with fluence in an exponential law, which was consistent with experimental results. The origin of hardness decrease after irradiation might be attributed to the break of Biv-O links that could be derived from the (1) decrease of average coordinate number of boron, (2) decrease of Si-O-Biv bonds, and (3) increase of non-bridging oxygen.
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In order to develop an effective and economical method for removing low concentration radioactive wastewater of uranium, the biomass of 'CMCC(F)-98003' Aspergillus niger was investigated in a batch system. The maximum uranium adsorption capacity of 12.5 mg g-1 was obtained at the initial uranium concentration of 0.75 mg L-1. The biosorption data on a biomass concentration of 0.029 g L-1 fitted well to the Freundlich isotherm with a correlation coefficient (R2) of 0.987. The calculated thermodynamic parameters showed that the biosorption of uranium ions was endothermic (ΔH° < 0). The results of scanning electron microscope and Fourier transform infrared spectrometry analysis revealed that nano-particles of uranium precipitation were formed on the cell surfaces after biosorption, and the functional groups of -CH, N-H, -COOH, P = O and the carbohydrates and alcohols were involved in the biosorption process between A. niger and uranium ions.
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Aspergillus niger/metabolismo , Urânio/metabolismo , Poluentes Radioativos da Água/metabolismo , Adsorção , Biodegradação Ambiental , Biomassa , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Eliminação de Resíduos LíquidosRESUMO
Microbial methylation and demethylation are two competing processes controlling the net production and bioaccumulation of neurotoxic methylmercury (MeHg) in natural ecosystems. Although mercury (Hg) methylation by anaerobic microorganisms and demethylation by aerobic Hg-resistant bacteria have both been extensively studied, little attention has been given to MeHg degradation by anaerobic bacteria, particularly the iron-reducing bacterium Geobacter bemidjiensis Bem. Here we report, for the first time, that the strain G. bemidjiensis Bem can mediate a suite of Hg transformations, including Hg(II) reduction, Hg(0) oxidation, MeHg production and degradation under anoxic conditions. Results suggest that G. bemidjiensis utilizes a reductive demethylation pathway to degrade MeHg, with elemental Hg(0) as the major reaction product, possibly due to the presence of genes encoding homologues of an organomercurial lyase (MerB) and a mercuric reductase (MerA). In addition, the cells can strongly sorb Hg(II) and MeHg, reduce or oxidize Hg, resulting in both time and concentration-dependent Hg species transformations. Moderate concentrations (10-500 µM) of Hg-binding ligands such as cysteine enhance Hg(II) methylation but inhibit MeHg degradation. These findings indicate a cycle of Hg methylation and demethylation among anaerobic bacteria, thereby influencing net MeHg production in anoxic water and sediments.
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Poluentes Ambientais/metabolismo , Geobacter/metabolismo , Mercúrio/metabolismo , Anaerobiose , Biodegradação Ambiental , Cisteína/química , Poluentes Ambientais/química , Ferro/metabolismo , Liases/metabolismo , Mercúrio/química , Metilação , Compostos de Metilmercúrio/metabolismo , Oxirredução , Oxirredutases/metabolismoRESUMO
Magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) experiments and molecular dynamics (MD) simulations were employed to investigate Na2O-B2O3-SiO2 and MgO-Na2O-B2O3-SiO2 glass structures up to ≈0.3 nm. This encompassed the {Na[p]}, {Mg[p]}, and {B[3], B[4]} speciations and the {Si, B[p], M[p]}-BO and {Si, B[p], M[p]}-NBO interatomic distances to the bridging oxygen (BO) and nonbridging oxygen (NBO) species, where the superscript indicates the coordination number. The MD simulations revealed the dominance of Mg[5] coordinations, as mirrored in average Mg2+ coordination numbers in the 5.2-5.5 range, which are slightly lower than those of the larger Na+ cation but with a narrower coordination distribution stemming from the higher cation field strength (CFS) of the smaller divalent Mg2+ ion. We particularly aimed to elucidate such Na+/Mg2+ CFS effects, which primarily govern the short-range structure but also the borosilicate (BS) glass network order, where both MD simulations and heteronuclear double-resonance 11B/29Si NMR experiments revealed a reduction of B[4]-O-Si linkages relative to B[3]-O-Si upon Mg2+-for-Na+ substitution. These effects were quantified and discussed in relation to previous literature on BS glasses, encompassing the implications for simplified structural models and descriptions thereof.
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Cancer has become one of the most important factors threatening human health, and the global cancer burden has been increasing rapidly. Immunotherapy has become another clinical research hotspot after surgery, chemotherapy, and radiotherapy because of its high efficiency and tumor metastasis prevention. However, problems such as lower immune response rate and immune-related adverse reaction in the clinical application of immunotherapy need to be urgently solved. With the development of nanodrug delivery systems, various nanocarrier materials have been used in the research of antitumor immunotherapy with encouraging therapeutic results. In this review, we mainly summarized the combination of nanodrug delivery systems and immunotherapy from the following 4 aspects: (a) nanodrug delivery systems combined with cytokine therapy to improve cytokines delivery in vivo; (b) nanodrug delivery systems provided a suitable platform for the combination of immune checkpoint blockade therapy with other tumor treatments; (c) nanodrug delivery systems helped deliver antigens and adjuvants for tumor vaccines to enhance immune effects; and (d) nanodrug delivery systems improved tumor treatment efficiency and reduced toxicity for adoptive cell therapy. Nanomaterials chosen by researchers to construct nanodrug delivery systems and their function were also introduced in detail. Finally, we discussed the current challenges and future prospects in combining nanodrug delivery systems with immunotherapy.
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BACKGROUND: "Gansui Banxia decoction" (GBD) is a classical traditional Chinese medicine formula for treating abnormal accumulation of fluid, such as malignant ascites (MA). Although GBD has shown definite water-expelling effects, its exact underlying mechanism has not been elucidated. PURPOSE: This study aimed to investigate the drug effects of GBD on MA rats and its underlying mechanisms. METHODS: The main chemical composition was determined by ultra-high performance liquid chromatography. The drug effects of GBD was evaluated in the established cancer cell-induced MA rat model. The symptoms were analyzed, and biological samples were collected for detecting immune and inflammation-related indicators by enzyme-linked immunosorbent assays, western blot, and flow cytometry. RESULTS: GBD increased urine discharge, decreased ascites production, and alleviated cachexia. After GBD treatment, the expression of TLR4, MyD88, and NF-кB and the release of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were reduced. In addition, GBD increased G1 phase arrest and inhibit excessive proliferation of cells in bone marrow while alleviating G1 phase arrest and increasing proliferation of cells in the thymus. Correspondingly, the development and maturation of T cells also changed. GBD increased the proportion of mature T-cells (CD4+CD8- and CD4-CD8+ single-positive (SP) T-cells), and decrease the proportion of immature cells (CD4+CD8+ double-positive (DP) T-cells and CD4-CD8- double-negative (DN) T-cells) in the blood or tumor microenvironment (TME, the ascites microenvironment). Finally, we further analysis of immune cell subsets, GBD decreased the proportion of immunosuppressive T-cells in the blood (CD4+CD25+Foxp3+T-cells) and TME (CD8+CD25+Foxp3+T-cells), and increased the proportion of anti-tumor immune cells (CD8+CD28+T-cells and NK cells) in the TME. CONCLUSION: These findings indicated that the drug effects of GBD were attributed to regulating the immune-inflammatory homeostasis, thereby mitigating the destruction of cancer cells and reducing the generation of ascites, which provided theoretical support for the clinical rational application and extended the scientific connotation of "water-expelling" of GBD.
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Ascite , Linfócitos T , Ratos , Animais , Ascite/tratamento farmacológico , Citocinas , Fator de Necrose Tumoral alfa , Fatores de Transcrição Forkhead , ÁguaRESUMO
Purpose: With the increase in prevalence and decrease in age of the obese population, safer weight loss methods have attracted growing attention. While abdominal massage (AM) has been clinically proven for weight loss, the mechanism thereof has yet to be elucidated. We aimed to investigate the effect of AM on abdominal fat in obese mice fed a high-fat diet and explore the possible mechanisms involved. Materials and Methods: Male C57BL/6J mice were fed a high-fat diet for 16 weeks and then treated with AM for 5 weeks; mice fed a standard diet were used as normal controls. Blood and adipose tissue, including inguinal white adipose tissue (WAT) and epididymal WAT, were collected from the mice after the intervention. We explored the mechanism of weight reduction through inguinal WAT transcriptome sequencing, quantitative real-time polymerase chain reaction (PCR) validation, and Western blot. Results: The results revealed that AM decreased fat mass, weight, glucose, and serum lipid levels. Meanwhile, AM enhanced the expression of the peroxisome proliferator-activated receptor gamma (PPARγ) and other downstream genes (Fabp4, Acox3, Pck1, and Aqp7) in inguinal WAT. In addition, AM increased the expression of PPARγ protein. Conclusion: AM may promote fatty acid oxidation, lipid metabolism, and glucose homeostasis by activating the PPARγ signaling pathway in inguinal WAT, thereby exhibiting therapeutic efficacy against obesity, even in the presence of a persistent high-fat diet.
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Atherosclerosis as the leading cause of the cardiovascular disease is closely related to cholesterol deposition within subendothelial areas of the arteries. Significantly, early atherosclerosis intervention is the critical phase for its reversal. As atherosclerosis progresses, early foam cells formation may evolve into fibrous plaques and atheromatous plaque, ulteriorly rupture of atheromatous plaque increases risks of myocardial infarction and ischemic stroke, resulting in high morbidity and mortality worldwide. Notably, amphiphilic apolipoproteins (Apos) can concomitantly combine with lipids to form soluble lipoproteins that have been demonstrated to associate with atherosclerosis. Apos act as crucial communicators of lipoproteins, which not only can mediate lipids metabolism, but also can involve in pro-atherogenic and anti-atherogenic processes of atherosclerosis via affecting subendothelial retention and aggregation of low-density lipoprotein (LDL), oxidative modification of LDL, foam cells formation and reverse cholesterol transport (RCT) in macrophage cells. Correspondingly, Apos can be used as endogenous and/or exogenous targeting agents to effectively attenuate the development of atherosclerosis. The article reviews the classification, structure, and relationship between Apos and lipids, how Apos serve as communicators of lipoproteins to participate in the pathogenesis progression of early atherosclerosis, as well as how Apos as the meaningful targeting mass is used in early atherosclerosis treatment.
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Apolipoproteínas , Aterosclerose , Placa Aterosclerótica , Humanos , Apolipoproteínas/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Colesterol/metabolismo , Lipoproteínas/metabolismo , Lipoproteínas LDL/química , Lipoproteínas LDL/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismoRESUMO
PURPOSE: The aim of the present study was to investigate the injuries of spleen and intestinal immune system induced by 2 Gy 60Co γ ray in mice. MATERIALS AND METHODS: A total of 120 Balb/c mice were randomly divided into two groups: blank control (Ctrl) and model (IR). The IR mice were exposed to a single dose of total body irradiation (2 Gy, dose rate: 1 Gy/min) and sacrificed on 1st, 3rd, 7th, 14th and 21st day after irradiation. The indicators including general observations and body weight, the changes in peripheral hemogram, spleen index, histopathology examination and lymphocyte subsets of spleen. As well as the count and subsets of lymphocyte in gut-associated lymphoid tissue. RESULTS: Compared with the Ctrl group, the body weight, spleen index, peripheral blood cell and splenocyte amounts, intraepithelial lymphocytes number decreased significantly after exposure, accompanied by a notable decreased count of lymphocytes in Peyer's patch and mesenteric lymph nodes. Moreover, ionizing radiation also broke the balance of CD4+/CD8+ and increased the Treg proportion in spleen, which then triggered immune imbalance and immunosuppression. In general, the spleen injuries occurred on 1st day after exposure, worse on 3rd day, and were relieved on 7th day. The intestinal immune injuries were observed on 1st day, and attenuated on 3rd day. On 21st day after exposure, the spleen volume and index have returned to normal, except for the distribution of lymphocyte subpopulations. Furthermore, all indicators of gut-associated lymphoid tissue, except for mesenteric lymph nodes lymphocyte count, had returned to normal levels on 21st day. CONCLUSION: In conclusion, our data showed the injuries of spleen and intestinal immune system induced by 2 Gy 60Co γ ray whole-body irradiation. These findings may provide the bases for further radiation protection in the immunity.