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A reliable method for determination of six α-dicarbonyl compounds in traditional Chinese medicines was first developed and validated by high-performance liquid chromatography-fluorescence detector with pre-column derivatization. α-Dicarbonyl compounds in traditional Chinese medicines were extracted and derivatized with 2,3-diaminaphthalene. The derivatization procedure of six α-dicarbonyl compounds was confirmed by high-resolution mass spectrometry. The limits of quantitation for six α-dicarbonyl compounds ranged from 3.70 × 10-3 to 2.21 × 10-2 µM. The established method showed good linearity (regression coefficient > 0.9990), precision (relative standard deviation < 3.37%), and high recovery (97.8%â¼113.1%). The developed method was successfully applied to detect the six α-dicarbonyl compounds in traditional Chinese medicines. The result exhibited six α-dicarbonyl compounds was found in the 15 kinds of traditional Chinese medicines, which suggested us that the determination of α-dicarbonyl compounds should be paid more attention in the quality control of traditional Chinese medicines.
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Medicina Tradicional Chinesa , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de MassasRESUMO
This randomized, multicenter, phase II clinical trial was performed to compare the safety and efficacy of concurrent chemoradiotherapy using S-1 (CCRT) with radiotherapy alone (RT) for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). All eligible patients were randomly assigned to the CCRT group or the RT group at a 1:1 ratio. The CCRT group received 50.4 Gy radiotherapy concurrent with S-1 and the RT group received 59.4 Gy radiotherapy alone. The primary endpoints were toxicity and the overall response rate (ORR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). In total, 157 elderly patients with ESCC were recruited from December 2016 to March 2020. By June 2021, the median follow-up duration had reached 38 months. No grade 5 toxicities occurred in either group and the overall rate of severe toxicities (≥grade 3) was higher in the CCRT group (19.2% vs 7.6%; P = .037), particularly neutropenia (7.7% vs 1.3%; P = .06). The CCRT group presented a significantly higher ORR (83.3% vs 68.4%; P = .009) and prolonged PFS (25.7 vs 13.9 months; P = .026) than the RT group. The median OS was 27.3 months in the CCRT group and 19.1 months in the RT group (P = .59). For patients older than 70 years with locally advanced ESCC, concurrent chemoradiotherapy with S-1 had tolerable adverse effects and improved ORR and PFS compared to radiotherapy alone.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Células Epiteliais/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , HumanosRESUMO
Diterpenoids are considered the major bioactive components in Scutellaria barbata to treat cancer and inflammation, but few comprehensive profiling studies of diterpenoids have been reported. Herein, a stepwise diagnostic product ions (DPIs) filtering strategy for efficient and targeted profiling of diterpenoids in Scutellaria barbata was developed using UHPLC-Q-Exactive-Orbitrap-MS. After UHPLC-HRMS/MS analysis of six diterpenoid reference standards, fragmentation behaviors of these references were studied to provide DPIs. Then, stepwise DPIs filtering aimed to reduce the potential interferences of matrix ions and achieve more chromatographic peaks was conducted to rapidly screen the diterpenoids. The results demonstrated that stepwise DPIs were capable of simplifying the workload in data post-processing and the effective acquisition of low abundance compounds. Subsequently, DPIs and MS/MS fragment patterns were adopted to identify the targeted diterpenoids. As a result, 381 diterpenoids were unambiguously or tentatively identified, while 141 of them with completely new molecular weights were potential new diterpenoids for Scutellaria barbata. These results demonstrate that the developed stepwise DPIs filtering method could be employed as an efficient, reliable, and valuable strategy to screen and identify the diterpenoid profile in Scutellaria barbata. This might accelerate and simplify target constituent profiling from traditional Chinese medicine (TCM) extracts.
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Diterpenos , Medicamentos de Ervas Chinesas , Scutellaria , Scutellaria/química , Espectrometria de Massas em Tandem/métodos , Diterpenos/química , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Íons , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The adult heart retains a limited ability to regenerate in response to injury. Although exercise can reduce cardiac ischaemia/reperfusion (I/R) injury, the relative contribution of cardiac cell proliferation including newly formed cardiomyocytes remains unclear. A 4-week swimming murine model was utilized to induce cardiac physiological growth. Simultaneously, the antineoplastic agent 5-fluorouracil (5-FU), which acts during the S phase of the cell cycle, was given to mice via intraperitoneal injections. Using EdU and Ki-67 immunolabelling, we showed that exercise-induced cardiac cell proliferation was blunted by 5-FU. In addition, the growth of heart in size and weight upon exercise was unaltered, probably due to the fact that exercise-induced cardiomyocyte hypertrophy was not influenced by 5-FU as demonstrated by wheat germ agglutinin staining. Meanwhile, the markers for pathological hypertrophy, including ANP and BNP, were not changed by either exercise or 5-FU, indicating that physiological growth still developed in the presence of 5-FU. Furthermore, we showed that CITED4, a key regulator for cardiomyocyte proliferation, was blocked by 5-FU. Meanwhile, C/EBPß, a transcription factor responsible for both cellular proliferation and hypertrophy, was not altered by treatment with 5-FU. Importantly, the effects of exercise in reducing cardiac I/R injury could be abolished when cardiac cell proliferation was attenuated in mice treated with 5-FU. In conclusion, cardiac cell proliferation is not necessary for exercise-induced cardiac physiological growth, but it is required for exercise-associated protection against I/R injury.
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Fluoruracila/farmacologia , Traumatismo por Reperfusão Miocárdica/terapia , Miócitos Cardíacos/efeitos dos fármacos , Condicionamento Físico Animal , Fase S/efeitos dos fármacos , Fatores de Transcrição/antagonistas & inibidores , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Fase S/genética , Transdução de Sinais , Natação , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
As a promising method for treating intractable epilepsy, the inhibitory effect of low-frequency stimulation (LFS) is well known, although its mechanisms remain unclear. Excessive levels of cerebral glutamate are considered a crucial factor for epilepsy. Therefore, we designed experiments to investigate the crucial parts of the glutamate cycle. We evaluated glutamine synthetase (GS, metabolizes glutamate), glutaminase (synthesizes glutamate), and glutamic acid decarboxylase (GAD, a γ-aminobutyric acid [GABA] synthetase) in different regions of the brain, including the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus, and the cortex, using western blots, immunohistochemistry, and enzyme activity assays. Additionally, the concentrations of glutamate, GABA, and glutamine (a product of GS) were measured using high-performance liquid chromatography (HPLC) in the same subregions. The results indicated that a transiently promoted glutamate cycle was closely involved in the progression from focal to generalized seizure. Low-frequency stimulation (LFS) delivered to the ventral hippocampus had an antiepileptogenic effect in rats exposed to amygdaloid-kindling stimulation. Simultaneously, LFS could partly reverse the effects of the promoted glutamate cycle, including increased GS function, accelerated glutamate-glutamine cycling, and an unbalanced glutamate/GABA ratio, all of which were induced by amygdaloid kindling in the DG when seizures progressed to stage 4. Moreover, glutamine treatment reversed the antiepileptic effect of LFS with regard to both epileptic severity and susceptibility. Our results suggest that the effects of LFS on the glutamate cycle may contribute to the antiepileptogenic role of LFS in the progression from focal to generalized seizure.
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Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Excitação Neurológica/metabolismo , Convulsões/metabolismo , Animais , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Giro Denteado/metabolismo , Progressão da Doença , Estimulação Elétrica , Glutamato Descarboxilase/metabolismo , Glutamina/metabolismo , Hipocampo/fisiopatologia , Excitação Neurológica/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Convulsões/fisiopatologia , Ácido gama-Aminobutírico/metabolismoRESUMO
An effective method for the simultaneous determination of docosahexaenoic acid and eicosapentaenoic acid in common seafood by gas chromatography was developed and validated. Total docosahexaenoic acid and eicosapentaenoic acid were extracted from seafood by ultrasonic cell crusher assisted extraction and methyl esterified for gas chromatography analysis in the presence of the internal standard. The linearity was good (r > 0.999) in 9.59 â¼ 479.5 µg/mL for docosahexaenoic acid and 9.56 â¼ 477.8 µg/mL for eicosapentaenoic acid. The intrarun and interrun precisions were both within 4.8 and 6.1% for the two analytes, while the accuracy was less than 5.8%. The developed method was applied for determination of docosahexaenoic acid and eicosapentaenoic acid in six kinds of seafood. The result showed the content of docosahexaenoic acid and eicosapentaenoic acid was all higher than 1 mg/g in yellow croaker, hairtail, venerupis philippinarum, mussel, and oyster. Our work may be helpful for dietary optimization and production of docosahexaenoic acid and eicosapentaenoic acid.
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Cromatografia Gasosa , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análise , Análise de Alimentos/métodos , Alimentos Marinhos/análise , UltrassomRESUMO
A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C18 column (4.6 × 150 mm, 5 µm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet.
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Antraquinonas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Flavonoides , Gastroenteropatias/metabolismo , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Antraquinonas/sangue , Antraquinonas/química , Antraquinonas/farmacocinética , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/sangue , Flavonoides/química , Flavonoides/farmacocinética , Motilidade Gastrointestinal , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
Objective: To identify the main chemical constituents and to determine the content in Feifukang mistura. Methods: HPLC-MS technique was used to profile and identify the chemical constituents by comparing the retention time,MS data with the reference standard. The content determination of all the chemical constituents were carried on a HPLC system. Results: Five compounds were separated from Feifukang mistura,which were identified as neomangiferin,mangiferin,calycosin-7-O-glucoside,calycosin,and schizandrol A. The standard curves of them showed good linearity on the range of 2. 08 ~ 104. 0 µg/m L,2. 00 ~ 100. 0 µg/m L,2. 00 ~ 100. 0µg/m L,2. 09 ~ 104. 5 µg/m L,and 1. 98 ~ 99. 0 µg/m L,respectively. The average recoveries were all in the range of 91. 3 ~ 103. 8%. Conclusion: The methods of chemical constituents identification and content determination were established,which may offer better revealing the material basis and controlling quality of Feifukang mistura.
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INTRODUCTION: The suppressing effects of chronic stress on sexual desire have long been noted. Yet the biological mechanisms underlying such effects, especially at the level of cellular biology of testicular cells, have not been fully investigated. AIM: In the present study, we used a chronic unpredictable mild stress model to examine the association between chronic stress and structural alterations in the male reproductive system. MAIN OUTCOME MEASURES: The main outcome measures were the structural changes in sperm cells and Leydig cells of male rats. We used Agmo and Ellingsen's procedure to study partner preference behavior and observed the morphology of Leydig cells and germ cells in the control and stress groups. METHODS: Our methods included histology, electron microscopy, and animal behavior tests. RESULTS: The results showed that after 5 weeks of chronic stress exposure, partner preference behavior was impaired, the total surface area of Leydig cells and the number and diameter of seminiferous tubules decreased significantly, and the number and size of Leydig cells, as well as the number and the short-axis diameter of spermatogenic cells, also decreased. At the ultrastructural level, transmission electron microscopy revealed that the basement membranes of seminiferous tubules in stressed rats was far thinner, had a low density, and was uneven in thickness compared with the normal group, with enhanced apoptosis in germ cells. CONCLUSION: We conclude that chronic stress can trigger organic damage to testicular cells in male rats.
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Doenças dos Genitais Masculinos/patologia , Células Intersticiais do Testículo/patologia , Motivação/fisiologia , Túbulos Seminíferos/patologia , Comportamento Sexual Animal/fisiologia , Estresse Psicológico/psicologia , Animais , Apoptose/efeitos dos fármacos , Estro/fisiologia , Feminino , Doenças dos Genitais Masculinos/psicologia , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espermatozoides/patologia , Estresse Psicológico/patologiaRESUMO
Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.
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Quimiocina CCL2 , Modelos Animais de Doenças , Jejum , Imiquimode , Monócitos , Psoríase , Animais , Psoríase/imunologia , Psoríase/induzido quimicamente , Psoríase/patologia , Monócitos/imunologia , Monócitos/metabolismo , Camundongos , Jejum/sangue , Quimiocina CCL2/metabolismo , Células Th17/imunologia , Interleucina-17/metabolismo , Pele/patologia , Pele/imunologia , Humanos , Camundongos Endogâmicos C57BL , Masculino , Proliferação de Células , Restrição Calórica , Jejum IntermitenteRESUMO
OBJECTIVE: This study aims to explore the common genetic basis between respiratory diseases and to identify shared molecular and biological mechanisms. METHODS: This genome-wide pleiotropic association study uses multiple statistical methods to systematically analyse the shared genetic basis between five respiratory diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung cancer and snoring) using the largest publicly available genome wide association studies summary statistics. The missions of this study are to evaluate global and local genetic correlations, to identify pleiotropic loci, to elucidate biological pathways at the multiomics level and to explore causal relationships between respiratory diseases. Data were collected from 27 November 2022 to 30 March 2023 and analysed from 14 April 2023 to 13 July 2023. MAIN OUTCOMES AND MEASURES: The primary outcomes are shared genetic loci, pleiotropic genes, biological pathways and estimates of genetic correlations and causal effects. RESULTS: Significant genetic correlations were found for 10 paired traits in 5 respiratory diseases. Cross-Phenotype Association identified 12 400 significant potential pleiotropic single-nucleotide polymorphism at 156 independent pleiotropic loci. In addition, multitrait colocalisation analysis identified 15 colocalised loci and a subset of colocalised traits. Gene-based analyses identified 432 potential pleiotropic genes and were further validated at the transcriptome and protein levels. Both pathway enrichment and single-cell enrichment analyses supported the role of the immune system in respiratory diseases. Additionally, five pairs of respiratory diseases have a causal relationship. CONCLUSIONS AND RELEVANCE: This study reveals the common genetic basis and pleiotropic genes among respiratory diseases. It provides strong evidence for further therapeutic strategies and risk prediction for the phenomenon of respiratory disease comorbidity.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Doenças Respiratórias/genética , Pleiotropia Genética , Doença Pulmonar Obstrutiva Crônica/genética , Asma/genéticaRESUMO
PURPOSE: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis. METHODS: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry. RESULTS: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues. CONCLUSIONS: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 âcells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.
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Acute myeloid leukemia (AML) is one of the most common types of blood cancer in adults and is associated with a poor survival rate. NK cells play a crucial role in combating AML, and alterations in immune checkpoint expression can impair NK cell function against AML. Targeting certain checkpoints may restore this function. CD96, an inhibitory immune checkpoint, has unclear expression and roles on NK cells in AML patients. In this study, we initially evaluated CD96 expression and compared CD96+ NK with the inhibitory receptor and stimulatory receptors on NK cells from AML patients at initial diagnosis. We observed increased CD96 expression on NK cells with dysfunctional phenotype. Further analysis revealed that CD96+ NK cells had lower IFN-γ production than CD96- NK cells. Blocking CD96 enhanced the cytotoxicity of primary NK and cord blood-derived NK (CB-NK) cells against leukemia cells. Notably, patients with a high frequency of CD96+ NK cells at initial diagnosis exhibited poorer clinical outcomes. Additionally, TGF-ß1 was found to enhance CD96 expression on NK cells via SMAD3 signaling. These findings suggest that CD96 is invovled in NK dysfunction against AML blast, and might be a potential target for restoring NK cell function in the fight against AML.
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BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. METHODS: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. RESULTS: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. CONCLUSIONS: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.
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Regulatory T (Treg) cells are essential for maintaining self-immune tolerance. Reduced numbers or functions of Treg cells have been involved in the pathogenesis of various autoimmune diseases and allograft rejection. Therefore, the approaches that increase the pool or suppressive function of Treg cells in vivo could be a general strategy to treat different autoimmune diseases and allograft rejection. Interleukin-2 (IL-2) is essential for the development, survival, maintenance, and function of Treg cells, constitutively expressing the high-affinity receptor of IL-2 and sensitive response to IL-2 in vivo. And low-dose IL-2 therapy in vivo could restore the imbalance between autoimmune response and self-tolerance toward self-tolerance via promoting Treg cell expansion and inhibiting follicular helper T (Tfh) and IL-17-producing helper T (Th17) cell differentiation. Currently, low-dose IL-2 treatment is receiving extensive attention in autoimmune disease and transplantation treatment. In this review, we summarize the biology of IL-2/IL-2 receptor, the mechanisms of low-dose IL-2 therapy in autoimmune diseases, the application in the progress of different autoimmune diseases, including Systemic Lupus Erythematosus (SLE), Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Autoimmune Hepatitis (AIH), Alopecia Areata (AA), Immune Thrombocytopenia (ITP) and Chronic graft-versus-host-disease (GVHD). We also discuss the future directions to optimize low-dose IL-2 treatments.
Low-dose interleukin-2 (IL-2) is a potential treatment for autoimmune diseases. IL-2 is a protein that helps regulate the immune system, and low doses of it can activate regulatory T cells (Tregs), which help control the immune response. This can be beneficial in autoimmune diseases where the immune system attacks healthy tissues. We discuss several clinical trials that have investigated the effectiveness of low-dose IL-2 in treating autoimmune diseases. These trials have shown promising results, with some patients experiencing improvements in symptoms and disease progression. However, more research is needed to determine the safety and effectiveness of low-dose IL-2 as a treatment for autoimmune diseases. IL-2 can also activate other immune cells, which may cause unwanted side effects. Therefore, careful monitoring and dosing are necessary when using this treatment. We should also take note of some of the challenges associated with using low-dose IL-2 as a treatment for autoimmune diseases. For example, it can be difficult to determine the optimal dose and dosing schedule for each patient. In addition, there may be individual differences in how patients respond to low-dose IL-2 treatment. Overall, we believe that low-dose IL-2 shows promise as a treatment for autoimmune diseases, but more research is needed to fully understand its potential benefits and risks.
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The paper aimed to evaluate the effects of dietary inclusion of green tea powder (GTP) on laying performance, egg quality, and blood biochemical parameters of laying hens. A total of 240 Jingfen No. 6 laying hens (age, 24 wk) were randomly allocated into 4 groups: control group (CON, basal diet), GTP0.5, GTP0.75, and GTP1.0 (basal diet included 0.5, 0.75, and 1.0% GTP, respectively). Each group has 5 replicates with 12 birds each. The feeding trial lasted 8 wk. The results showed that the hen-day egg production rate in GTP0.5 and GTP 0.75 group was higher than that of GTP1.0 group (P < 0.05), hen-day egg production rate in the GTP1.0 group was lower compared to the CON group (P > 0.05), the feed conversion ratio (FCR) in the GTP0.75 group was lower than that in CON and GTP 1.0 group (P < 0.05) during the entire experimental period. Albumen height and Haugh unit were higher in the GTP0.75 and GTP1.0 group compared to the CON group at d 56 (P < 0.05). At the end of experiment, plasma TG content in the GTP0.75 and GTP1.0 group was lower than that in the CON group (P < 0.05), the T-CH concentration in the GTP0.5 and GTP0.75 group was lower compared to the CON group (P < 0.05), plasma LDL-C and CORT concentrations were decreased by dietary GTP supplementation (P < 0.05), the HDL-C and BUN concentrations in the GTP0.75 and GTP1.0 group were higher than that in the CON group (P < 0.05). The antibody titers of H5N1 in the GTP0.75 and GTP1.0 group, and H7N9 in the GTP1.0 group were lower than that in the CON group (P < 0.05). In conclusion, dietary GTP inclusion could affect laying performance, regulate lipid metabolism, and have no favorable influence on antibody titers of H5N1 and H7N9, herein, dietary 0.5% GTP inclusion is suggested for Jingfen No. 6 laying hens during the peak laying period.
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Virus da Influenza A Subtipo H5N1 , Subtipo H7N9 do Vírus da Influenza A , Animais , Feminino , Suplementos Nutricionais , Galinhas/fisiologia , Pós , Chá , Óvulo , Dieta/veterinária , Guanosina Trifosfato , Ração Animal/análiseRESUMO
In this article, we performed symmetry analysis of perovskite-based multiferroics: bismuth ferrite (BiFeO3)-like, orthochromites (RCrO3), and Ruddlesden-Popper perovskites (Ca3Mn2O7-like), being the typical representatives of multiferroics of the trigonal, orthorhombic, and tetragonal crystal families, and we explored the effect of crystallographic distortions on magnetoelectric properties. We determined the principal order parameters for each of the considered structures and obtained their invariant combinations consistent with the particular symmetry. This approach allowed us to analyze the features of the magnetoelectric effect observed during structural phase transitions in BixR1-xFeO3 compounds and to show that the rare-earth sublattice has an impact on the linear magnetoelectric effect allowed by the symmetry of the new structure. It was shown that the magnetoelectric properties of orthochromites are attributed to the couplings between the magnetic and electric dipole moments arising near Cr3+ ions due to distortions linked with rotations and deformations of the CrO6 octahedra. For the first time, such a symmetry consideration was implemented in the analysis of the Ruddlesden-Popper structures, which demonstrates the possibility of realizing the magnetoelectric effect in the Ruddlesden-Popper phases containing magnetically active cations, and allows the estimation of the conditions required for its optimization.
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Psoriasis is a chronic autoimmune inflammatory disease that remains active for a long period, even for life in most patients. The impact of psoriasis on health is not only limited to the skin, but also influences multiple systems of the body, even mental health. With the increasing of literature on the association between psoriasis and extracutaneous systems, a better understanding of psoriasis as an autoimmune disease with systemic inflammation is created. Except for cardiometabolic diseases, gastrointestinal diseases, chronic kidney diseases, malignancy, and infections that have received much attention, the association between psoriasis and more systemic diseases, including the skin system, reproductive system, and oral and ocular systems has also been revealed, and mental health diseases draw more attention not just because of the negative mental and mood influence caused by skin lesions, but a common immune-inflammatory mechanism identified of the two systemic diseases. This review summarizes the epidemiological evidence supporting the association between psoriasis and important and/or newly reported systemic diseases in the past 5 years, and may help to comprehensively recognize the comorbidity burden related to psoriasis, further to improve the management of people with psoriasis.
Assuntos
Psoríase , Insuficiência Renal Crônica , Doença Crônica , Comorbidade , Humanos , Inflamação/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Pele/patologiaRESUMO
Objective: In contrast to normal cells, in which reactive oxygen species (ROS) are maintained in redox equilibrium, cancer cells are characterized by ectopic ROS accumulation. Myoferlin, a newly identified oncogene, has been associated with tumor metastasis, intracellular ROS production, and energy metabolism. The mechanism by which myoferlin regulates gastric cancer cell migration and ROS accumulation has not been determined. Methods: Myoferlin expression, intracellular ROS levels, the ratios of reduced to oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) and migratory ability were measured in gastric cancer cells in vitro and in the TCGA and GEO databases in silico. Results: Myoferlin was found to be more highly expressed in tumor than in normal tissues of gastric cancer patients, with higher expression of Myoferlin associated with shorter survival time. Myoferlin was associated with significantly higher intracellular ROS levels and enhanced migration of gastric cancer cells. N-acetyl-L-cysteine (NAC), a potent inhibitor of ROS, inhibited Myoferlin-induced ROS accumulation and cell migration. Conclusions: Myoferlin is a candidate prognostic biomarker for gastric cancer and plays an essential role in regulating redox equilibrium and gastric cancer cell migration. Myoferlin may also be a new target for treatment of patients with gastric cancer.
RESUMO
Obesity is regarded to be associated with fat accumulation, chronic inflammation, and gut microbiota dysbiosis. Raw and ripened pu-erh tea extract (PETe) have the effect of reducing body weight gain and fat accumulation, which are associated with gut microbiota. However, little is known about the difference of raw and ripened PETe on the regulation of gut microbiota. Here, our results suggested that supplementation of raw and ripened PETe displayed similar anti-obesogenic effect in high fat diet (HFD)-induced obesity mice, by attenuating the body weight gain, fat accumulation, oxidative injury, and low-grade inflammation, improving the glucose tolerance, alleviating the metabolic endotoxemia, and regulating the mRNA and protein expression levels of the lipid metabolism-related genes. 16S rRNA sequencing of fecal samples indicated that raw and ripened PETe intervention displayed different regulatory effect on the HFD-induced gut microbiota dysbiosis at different taxonomic levels. The microbial diversity, the relative abundance of Firmicutes and Bacteroidetes as well as F/B ratio were reversed more closer to normal by ripened PETe. Phylotypes of Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, Muribaculaceae, and Rikenellaceae which are negatively correlated with obesity were enhanced notably by the intervention of ripened PETe, while Erysipelotrichaceae and Lactobacillaceae which have positive correlation with obesity were decreased dramatically. In addition, the treatment of ripened PETe had better effect on the increase of benefical Bacteroides, Alistipes, and Akkemansia and decrease of obesity associated Faecalibaculum and Erysipelatoclostridium (p < 0.05). These findings suggested that pu-erh tea especially ripened pu-erh tea could serve as a great candidate for alleviation of obesity in association with the modulation of gut microbiota.