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OBJECTIVE: This study aimed to improve the efficiency of pharmacotherapy for CNS diseases by optimizing the ability of drug molecules to penetrate the Blood-Brain Barrier (BBB). METHODS: We established qualitative and quantitative databases of the ADME properties of drugs and derived characteristic features of compounds with efficient BBB penetration. Using these insights, we developed four machine learning models to predict a drug's BBB permeability by assessing ADME properties and molecular topology. We then validated the models using the B3DB database. For acyclovir and ceftriaxone, we modified the Hydrogen Bond Donors and Acceptors, and evaluated the BBB permeability using the predictive model. RESULTS: The machine learning models performed well in predicting BBB permeability on both internal and external validation sets. Reducing the number of Hydrogen Bond Donors and Acceptors generally improves BBB permeability. Modification only enhanced BBB penetration in the case of acyclovir and not ceftriaxone. CONCLUSIONS: The machine learning models developed can accurately predict BBB permeability, and many drug molecules are likely to have increased BBB penetration if the number of Hydrogen Bond Donors and Acceptors are reduced. These findings suggest that molecular modifications can enhance the efficacy of CNS drugs and provide practical strategies for drug design and development. This is particularly relevant for improving drug penetration of the BBB.
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Aciclovir , Barreira Hematoencefálica , Aprendizado de Máquina , Permeabilidade , Barreira Hematoencefálica/metabolismo , Humanos , Aciclovir/farmacocinética , Ligação de Hidrogênio , Ceftriaxona/farmacocinética , Fármacos do Sistema Nervoso Central/farmacocinética , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/metabolismo , Desenho de FármacosRESUMO
BACKGROUND: Primary pulmonary artery sarcoma (PAS) is an extremely rare malignant tumor with a poor prognosis. The clinical manifestations of PAS are diverse, including dyspnea, chest pain, cough, and hemoptysis. The poor prognosis is often due to delayed diagnosis caused by similarity in imaging findings with pulmonary thromboembolism (PTE). These cues of diagnosis include the "wall eclipsing sign", lobulated bulging margins, gadolinium enhancement during MRI imaging, and FDG uptake during PET/CT imaging. However, there are still many misdiagnoses. CASE PRESENTATION: This article reports a woman of reproductive age presenting with a pulmonary artery mass. The computed tomographic pulmonary angiography and positron emission tomography/computed tomography did not show obvious signs of pulmonary artery sarcoma, however, contrast-enhanced echocardiography showed moderate perfusion, which helped differentiate between pulmonary artery sarcoma and pulmonary artery thrombosis, leading to timely surgical treatment. CONCLUSIONS: PAS is a rare form of cancer that can occasionally be visually similar to PTE on radiographic images. Early diagnosis of PAS is of vital importance to the prognosis of the patients. There are several visual cues that can help differentiate between the two conditions. Additionally, contrast-enhanced echocardiography provides additional information on tumor perfusion, offering another effective approach for a prompt and accurate diagnosis.
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Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in SpragueâDawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.
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The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead to liver fibrosis injury in rats, while the precise pathogenic mechanism still requires further investigation. In the past few years, the Nod-like receptor protein 3 (NLRP3) inflammasome has been found to play a pivotal role in the occurrence and development of liver injury. In this study, we administered varying doses of sodium arsenite (NaAsO2) and 10â¯mg/kg.bw MCC950 (a particular tiny molecular inhibitor targeting NLRP3) to Sprague-Dawley (SD) rats for 36 weeks to explore the involvement of NLRP3 inflammasome in NaAsO2-induced liver injury. The findings suggested that prolonged exposure to NaAsO2 resulted in pyroptosis in liver tissue of SD rats, accompanied by the fibrotic injury, extracellular matrix (ECM) deposition and liver dysfunction. Moreover, long-term NaAsO2 exposure activated NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines in liver tissue. After treatment with MCC950, the induction of NLRP3-mediated pyroptosis and release of pro-inflammatory cytokines were significantly attenuated, leading to a decrease in the severity of liver fibrosis and an improvement in liver function. To summarize, those results clearly indicate that hepatic fibrosis and liver dysfunction induced by NaAsO2 occur through the activation of NLRP3 inflammasome-mediated pyroptosis, shedding new light on the potential mechanisms underlying arsenic-induced liver damage.
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Arsênio , Hepatopatias , Ratos , Animais , Inflamassomos/metabolismo , Ratos Sprague-Dawley , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR , Piroptose , Modelos Animais de Doenças , Fibrose , Cirrose Hepática/induzido quimicamente , Sulfonamidas/farmacologia , Citocinas/metabolismoRESUMO
It is well-known that the hepatotoxicity of drugs can significantly influence their clinical use. Despite their effective therapeutic efficacy, many drugs are severely limited in clinical applications due to significant hepatotoxicity. In response, researchers have created several machine learning-based hepatotoxicity prediction models for use in drug discovery and development. Researchers aim to predict the potential hepatotoxicity of drugs to enhance their utility. However, current hepatotoxicity prediction models often suffer from being unverified, and they fail to capture the detailed toxicological structures of predicted hepatotoxic compounds. Using the 56 chemical constituents of Gardenia jasminoides as examples, we validated the trained hepatotoxicity prediction model through literature reviews, principal component analysis (PCA), and structural comparison methods. Ultimately, we successfully developed a model with strong predictive performance and conducted visual validation. Interestingly, we discovered that the predicted hepatotoxic chemical constituents of Gardenia possess both toxic and therapeutic effects, which are likely dose-dependent. This discovery greatly contributes to our understanding of the dual nature of drug-induced hepatotoxicity.
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Bamboos are fast-growing, aggressively-spreading, and invasive woody clonal species that often encroach upon adjacent tree plantations, forming bamboo-tree mixed plantations. However, the effects of bamboo invasion on leaf carbon (C) assimilation, and nitrogen (N) and phosphorus (P) utilization characteristics remains unclear. We selected four different stands of Pleioblastus amarus invading Chinese fir (Cunninghamia lanceolata) plantations to investigate the concentrations, stoichiometry, and allometric growth relationships of mature and withered leaves of young and old bamboos, analyzing N and P utilization and resorption patterns. The stand type, bamboo age, and their interaction affected the concentrations, stoichiometry and allometric growth patterns of leaf C, N, and P in both old and young bamboos, as well as the N and P resorption efficiency. Bamboo invasion into Chinese fir plantations decreased leaf C, N, and P concentrations, C:N and C:P ratios, N and P resorption efficiency, and allometric growth exponents among leaf C, N, and P, while it only slightly altered N:P ratios. PLS-PM analysis revealed that bamboo invasion negatively impacted leaf C, N, and P concentrations, as well as N and P utilization and resorption. The results indicate that high N and P utilization and resorption efficiency, along with the mutual sharing of C, N, and P among bamboos in interface zones, promote continuous bamboo expansion and invasion. Collectively, these findings highlight the significance of N and P utilization and resorption in bamboo expansion and invasion and provide valuable guidance for the establishment of mixed stands and the ecological management of bamboo forests.
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Nitrogênio , Nitrogênio/metabolismo , Espécies Introduzidas , Fósforo/análise , Folhas de Planta/metabolismo , Carbono , Poaceae/crescimento & desenvolvimento , Nutrientes/metabolismo , Árvores , Cunninghamia/crescimento & desenvolvimento , Cunninghamia/metabolismo , Sasa/metabolismoRESUMO
We introduce a "solution-processing-transformation" strategy, deploying solvent vapor as scaffolds, to fabricate high-quality hydrogen-bonded organic framework (HOF) membranes. This strategy can overcome the mismatch in processing conditions and crystal growth thermodynamics faced during the facile solution processing of the membrane. The procedure includes the vapor-trigged in situ transformation of dense amorphous supramolecules to crystalline HOF-16, with HOF-11 as the transient state. The mechanism involves a vapor-activated dissolution-precipitation equilibrium shifting and hydrogen bonding-guided molecule rearrangement, elucidated through combined experimental and theoretical analysis. Upon removal of the molecular scaffolds, the resulting HOF-16 membranes showcase significant improvement in hydrogen separation performance over their amorphous counterparts and previously reported HOF membranes. The method's broad applicability is evidenced by successfully extending it to other substrates and HOF structures. This study provides a fundamental understanding of guest-induced ordered supramolecular assembly and paves the way for the advanced manufacture of high-performance HOF membranes for gas separation processes.
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The carbon emission problem is a significant challenge in today's society, which has led to severe global climate issues. Membrane-based separation technology has gained considerable interest in CO2 separation due to its simplicity, environmental friendliness, and energy efficiency. Crystalline porous materials (CPMs), such as zeolites, metal-organic frameworks, covalent organic frameworks, hydrogen-bonded organic frameworks, and porous organic cages, hold great promise for advanced CO2 separation membranes because of their ordered and customizable pore structures. However, the preparation of defect-free and large-area crystalline porous material (CPM)-based membranes remains challenging, limiting their practical use in CO2 separation. To address this challenge, the solution-processing method, commonly employed in commercial polymer preparation, has been adapted for CPM membranes in recent years. Nanosheets, spheres, molecular cages, and even organic monomers, depending on the CPM type, are dissolved in suitable solvents and processed into continuous membranes for CO2 separation. This feature article provides an overview of the recent advancements in the solution processing of CPM membranes. It summarizes the differences among the solution-processing methods used for forming various CPM membranes, highlighting the key factors for achieving continuous membranes. The article also summarizes and discusses the CO2 separation performance of these membranes. Furthermore, it addresses the current issues and proposes future research directions in this field. Overall, this feature article aims to shed light on the development of solution-processing techniques for CPM membranes, facilitating their practical application in CO2 separation.
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BACKGROUND: Periodontitis is a common complication of diabetes, with advanced glycation end products (AGEs) playing a key role in its pathogenesis. Albiflorin, a monoterpene glycoside, has shown potential anti-inflammatory and antioxidant properties. This study aims to investigate the effects of albiflorin on AGEs-induced gingival fibroblasts and its underlying mechanisms. OBJECTIVE: This study aimed to evaluate the role of albiflorin in mitigating ROS production, inflammation, and MMP-1 expression in AGEs-induced gingival fibroblasts. METHODS: The viability of gingival fibroblasts treated with albiflorin and AGEs was assessed using CCK-8 assays. ROS levels were measured by DCF staining, and the expression of inflammatory markers and MMP-1 was evaluated by ELISA and qPCR. The involvement of the NF-κB and Nrf2 pathways was examined by immunoblotting. RESULTS: Albiflorin enhanced the viability of AGEs-induced gingival fibroblasts and reduced ROS production. It also decreased the expression of IL-6, IL-8, RAGE, and MMP-1, suggesting an anti- inflammatory effect. Mechanistically, albiflorin modulated the NF-κB and Nrf2 pathways in AGEs-induced gingival fibroblasts. CONCLUSION: Albiflorin exhibited protective effects against AGEs-induced oxidative stress and inflammation in gingival fibroblasts, highlighting its potential as a therapeutic agent for periodontitis in diabetic patients. The modulation of the NF-κB and Nrf2 pathways by albiflorin provides insight into its mechanism of action.
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Trichohepatoenteric syndrome is a rare autosomal recessive genetic disease caused by TTC37 (also known as SKIC3) or SKIV2L gene variant. We present a severely affected 2-month-old male infant with recurrent fever and unexplained diarrhea. Additionally, clinical data of 11 patients with trichohepatoenteric syndrome in China from 1 to 60 days of onset was presented. The infant's condition was not substantially relieved after cefotaxime sulbactam and meropenem treatment. Whole-exome sequencing revealed compound heterozygous variants (c.1708C>T and c.3342-9T>G) in TTC37 of the child whose parents were heterozygous carriers of the corresponding locus. The c.3342-9T>G variant originated from his mother and was reported for the first time. Combined with the clinical manifestations, the infant was diagnosed with trichohepatoenteric syndrome and treated with ganciclovir antiviral, intravenous nutritional support, and liver function protection. The infant was discharged with no fever and high stool frequency, but his condition improved. Therefore, trichohepatoenteric syndrome should be considered for recurrent fever and unexplained diarrhea.
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Aeromonas hydrophila, an aquatic pathogenic bacterium, has been found to infect many fish species and cause huge aquaculture losses. Antibiotics are the most common drugs used to treat these infections. However, antibiotic abuse can lead to the development of antibiotic resistance. Probiotics have the potential to replace antibiotics for preventing infections. Zebrafish (Danio rerio) is a model organism used to study the innate immune system and host-pathogen interactions. Currently, there is little information on how the fish immune system responds to A. hydrophila and probiotic treatment. To increase the understanding of the molecular mechanisms behind the zebrafish defense against A. hydrophila and provide evidence that antibiotics can be replaced by probiotics, a transcriptome analysis of the zebrafish spleen was conducted 48 hours after infection by A. hydrophila, as well as after treatment using Lactococcus lactis KUST48 4 hours after infection. A total of 36,499 genes were obtained. There were 3,337 genes found to have significant differential expression between treatment and control groups. According to further annotation and enrichment analysis, differentially expressed genes (DEGs) were involved in signal transduction, endocrine system cancer, and the immune system. Insulin resistance disappeared in the zebrafish after treatment. Quantitative real-time PCR was performed to confirm the significant regulation of immune defense DEGs, the results of which were consistent with the RNA-sequencing data. These results could serve as a basis for future studies on the immune response to A. hydrophila and provide suggestions for probiotic alternatives to antibiotics, which will be of great significance to aquaculture and environmental protection.IMPORTANCEIn recent years, the unreasonable use of antibiotics has led to the emergence of drug-resistant pathogenic bacteria, antibiotic residues, cross infection, toxic side effects, and so on, which has caused a serious threat to human food safety and life health. In recent years, many studies have demonstrated the potential of probiotics as a substitute for antibiotics, but there is still a lack of understanding of the molecular mechanisms underlying probiotic therapy. We conduct a research on the impact of Lactococcus lactis KUST48 on the transcription profile of Aeromonas hydrophila-infected zebrafish spleen. Mortality of zebrafish infected with A. hydrophila was significantly reduced after treatment with L. lactis KUST48. Our results can help to strengthen our understanding of the pathogenic mechanisms of zebrafish and provide a valuable reference for the molecular mechanisms of probiotic therapy.
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Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Lactococcus lactis , Animais , Humanos , Peixe-Zebra , Aeromonas hydrophila/genética , Lactococcus lactis/genética , Baço , Antibacterianos , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/microbiologia , Doenças dos Peixes/microbiologiaRESUMO
OBJECTIVE: This study aims to explore the impact of ADME on the Oral Bioavailability (OB) of drugs and to construct a machine learning model for OB prediction. The model is then applied to predict the OB of modified berberine and atenolol molecules to obtain structures with higher OB. METHODS: Initially, a drug OB database was established, and corresponding ADME characteristics were obtained. The relationship between ADME and OB was analyzed using machine learning, with Morgan fingerprints serving as molecular descriptors. Compounds from the database were input into Random Forest, XGBoost, CatBoost, and LightGBM machine learning models to train the OB 7prediction model and evaluate its performance. Subsequently, berberine and atenolol were modified using Chemdraw software with ten different substituents for mono-substitution, and chlorine atoms for a full range of double substitutions. The modified molecular structures were converted into the same format as the training set for OB prediction. The predicted OB values of the modified structures of berberine and atenolol were compared. RESULTS: An OB database of 386 drugs was obtained. It was found that smaller molecular weight and a higher number of rotatable bonds (ten or less) could potentially lead to higher OB. The four machine learning models were evaluated using MSE, R2 score, MAE, and MFE as metrics, with Random Forest performing the best. The models' predictions for the test set were particularly accurate when OB ranged from 30% to 90%. After mono-substitution and double substitution of berberine and atenolol, the OB of both drugs was significantly improved. CONCLUSIONS: This study found that some ADME properties of molecules do not have an absolute impact on OB. The database played a decisive role in the process of the machine learning OB prediction model, and the performance of the model was evaluated based on predictions within a range of strong generalization ability. In most cases, mono-substitution and double substitution were beneficial for enhancing the OB of berberine and atenolol. In summary, this study successfully constructed a machine learning regression prediction model that can accurately predict drug OB, which can guide drug design to achieve higher OB to some extent.
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Atenolol , Berberina , Disponibilidade Biológica , Aprendizado de Máquina , SoftwareRESUMO
[This corrects the article DOI: 10.7150/thno.43198.].
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Arsenic, a poisonous metalloid element, is linked to liver diseases, but the exactmechanisms for this process are not yet to be completely elucidated. Toll like receptor 4 (TLR4), acting as a pathogenic pattern recognition receptor, plays a pivotal role in various inflammatory diseases via the myeloid differentiation factor 88 (MyD88) pathway. This study aims to investigate the involvement of the TLR4-MyD88 signaling pathway in liver injury induced by prolonged exposure to sodium arsenite (NaAsO2) in Sprague-Dawley rats. Our research findings demonstratethe activation of TLR4-MyD88 signaling pathway in long-term NaAsO2-exposed rat liver tissues, leading to a significant release of inflammatory factors, which suggests its potential involvement in the pathogenesis of NaAsO2-induced liver injury. We further administered lipopolysaccharide (LPS), a natural ligand of TLR4, and TAK-242, a specific inhibitor of TLR4, to rats in order to validate the specific involvement of the TLR4-MyD88 signaling pathway in NaAsO2-induced liver injury. The results showed that, 1 mg/kg.bw LPS treatment significantly activated TLR4-MyD88 signalling pathway and its mediated pro-inflammatory factors, leading to up-regulation of activation indicators in hepatic stellate cells (HSCs) as well as increased secretion levels of extracellular matrix (ECM) in the liver, and ultimately induced liver fibrosis and dysfunction in rats. Relevantly, subsequent administration of 0.5 mg/kg.bw TAK-242 significantly attenuated the expression levels of TLR4 and its associated proteins, mitigated collagen deposition, and partially improved liver fibrosis and dysfunction caused by NaAsO2 in rats. Our study fully confirms the pivotal role of the TLR4-MyD88 signaling in promoting liver injury induced by NaAsO2, thereby providing a novel molecular target for preventing and treating patients with arsenic poisoning-related liver injury.
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BACE1, a crucial enzyme in the amyloid-ß deposition theory of Alzheimer's disease (AD), is targeted by Codonopsis pilosula, a traditional tonic believed to impede AD onset. However, the specific active compounds responsible for its effects remain elusive. Our prior network pharmacology research identified C. pilosula polysaccharides (CPPS) and Lobetyolin may serve as potential inhibitors of AD by suppressing amyloidogenesis. Here, we recombinantly expressed BACE1 under varied conditions and assessed its activity using Fluorescence Resonance Energy Transfer technology. Through spectroscopy, molecular docking, and dynamics, we elucidated the interactions of CPPS, Lobetyolin, and BACE1. Optimal BACE1 expression occurred at 22⯰C with 0.4â¯mM IPTG for 6â¯h, yielding a 72â¯kDa protein. Enzyme kinetics displayed a maximum rate of 4096⯵mol/min and a Michaelis constant of 16â¯mg/mL for BACE1. Spectroscopic analysis revealed differing binding affinities of the compounds at various temperatures, peaking at 293â¯K. Lobetyolin exhibited superior binding to BACE1 compared to CPPS, driven by hydrophobic and electrostatic forces. Molecular docking and dynamics highlighted hydrophobic amino acids' role in BACE1 interactions with Lobetyolin and CPPS, with binding energy < -1.2â¯kcal/mol signifying strong affinities. Notably, Lobetyolin and CPPS showed higher BACE1 affinity than APP, with the Lobetyolin-BACE1 complex being the most stable.
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Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown. In our study, we uncovered a mechanism by which the contralateral kidney responded to injury. We found that the activation of mineralocorticoid receptors and the increase in vascular endothelial growth factor C in the contralateral kidney after unilateral ureteral obstruction could promote lymphangiogenesis. Furthermore, mineralocorticoid receptor activation in lymphatic endothelial cells resulted in the secretion of myofibroblast markers, thereby contributing to renal fibrosis. We observed that this process could be attenuated by administering the mineralocorticoid receptor blocker eplerenone, which, prevented the development of fibrotic injury in the contralateral kidneys of rats with unilateral ureteral obstruction. These findings offer valuable insights into the intricate mechanisms underlying kidney injury and may have implications for the development of therapeutic strategies to mitigate renal fibrosis in the context of kidney disease.
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Eplerenona , Fibrose , Rim , Linfangiogênese , Antagonistas de Receptores de Mineralocorticoides , Obstrução Ureteral , Animais , Eplerenona/farmacologia , Linfangiogênese/efeitos dos fármacos , Ratos , Fibrose/tratamento farmacológico , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia , Obstrução Ureteral/complicações , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Masculino , Receptores de Mineralocorticoides/metabolismo , Espironolactona/análogos & derivados , Espironolactona/farmacologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Ratos Sprague-Dawley , Miofibroblastos/metabolismo , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologiaRESUMO
Lung immune cells such as lymphocytes and macrophages can induce an inflammatory response due to the activation of mineralocorticoid receptor (MR), which is manifested by the infiltration of inflammatory cells and the secretion of inflammatory cytokines and subsequent apoptosis, pyroptosis and necrosis of intrinsic lung cells and immune cells. Macrophages are immune cells that are abundant in the lung and act as the first line of defense against pathogens but are also aggravating factors of infection. The activation of the renin-angiotensin-aldosterone system (RAAS), especially aldosterone-stimulated MR activation, can induce macrophage and CD8+ T cell aggregation and the secretion of cytokines such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ). Increased IFN-γ secretion can induce macrophage pyroptosis and the release of interleukin 1-ß (IL-1ß), aggravating lung injury. In this study, lung injury in C57BL/6 mice was induced by subcutaneous micro-osmotic pump infusion of aldosterone. After 12 weeks of administration, the kidney, heart, blood vessels and lungs all showed obvious inflammatory injury, which manifested as rapid accumulation of macrophages. The overexpression of IFN-γ in the lungs of aldosterone-treated mice and the stimulation of MH-S and RAW264.7 alveolar macrophages (AMs) with aldosterone in vitro showed that IFN-γ induced pyroptosis of macrophages via the activation of the inflammasome, and the MR blocker esaxerenone effectively inhibited this effect and alleviated lung injury. In addition, IFN-γ secreted by CD8+ T cells is associated with macrophage pyroptosis. In conclusion, the inhibition of macrophage pyroptosis can effectively alleviate lung injury.
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Gastric cancer is one of the most common malignant tumors worldwide and has a high mortality rate. However, tests for the early screening and diagnosis of gastric cancer are limited and invasive. Certain oral microorganisms are over-expressed in gastric cancer, but there is heterogeneity among different studies. Notably, each oral ecological niche harbors specific microorganisms. Among them, tongue coating, saliva, and dental plaque are important and unique ecological niches in the oral cavity. The colonization environment in different oral niches may be a source of heterogeneity. In this paper, we systematically discuss the latest developments in the field of the oral microbiota and gastric cancer and elucidate the enrichment of microorganisms in the oral ecological niches of the tongue coatings, saliva, and dental plaque in gastric cancer patients. The various potential mechanisms by which the oral microbiota induces gastric cancer (activation of an excessive inflammatory response; promotion of proliferation, migration, invasion, and metastasis; and secretion of carcinogens, leading to imbalance in gastric microbial communities) are explored. In this paper, we also highlight the applications of the rapeutics targeting the oral microbiota in gastric cancer and suggests future research directions related to the relationship between the oral microbiota and gastric cancer.
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ETHNOPHARMACOLOGICAL RELEVANCE: Lablab Semen Album (lablab), the white and dried mature fruit of Lablab purpureus in the Lablab genus of the Fabaceae family, is a renowned traditional medicinal herb with a long history of use in China. In Chinese medicine, lablab is often combined with other drugs to treat conditions such as weak spleen and stomach, loss of appetite, loose stools, excessive leucorrhoea, summer dampness and diarrhea, chest tightness, and abdominal distension. MATERIALS AND METHODS: Comprehensive information on lablab was gathered from databases including Web of Science, Science Direct, Google Scholar, Springer, PubMed, CNKI, Wanfang, and ancient materia medica. RESULTS: Lablab, a member of the lentil family, thrives in warm and humid climates, and is distributed across tropical and subtropical regions worldwide. Traditionally, lablab is used to treat various ailments, such as spleen and stomach weakness, loss of appetite, and diarrhea. Phytochemical analyses reveal that lablab is a rich source of triterpenoid saponins, glucosides, volatile components, polysaccharides, and amino acids. Lablab extracts exhibit diverse biological activities, including hypolipidemic, hypoglycemic, immunomodulatory, antioxidant, hepatoprotective, antitumoral, antiviral properties, and more. Besides its medicinal applications, lablab is extensively used in the food industry due to its high nutrient content. Additionally, the quality of lablab can be regulated by determining the levels of key chemical components pivotal to its medicinal effects, ensuring the herb's overall quality. CONCLUSION: Lablab is a promising medicinal and edible plant ingredient with diverse pharmacological effects, making it a valuable ingredient for food, pharmaceuticals, and animal husbandry. However, it has inherent toxicity if not properly prepared. Additionally, some traditional uses and pharmacological activities lack scientific validation due to incomplete methods, unclear results, and insufficient clinical data. Thus, further in vivo and in vitro studies on its pharmacology, pharmacokinetics, and toxicology, along with clinical efficacy evaluations, are needed to ensure lablab's safety and effectiveness. As an important traditional Chinese medicine, lablab deserves more attention.
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Etnofarmacologia , Controle de Qualidade , Humanos , Animais , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , FitoterapiaRESUMO
CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.