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OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 107 CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- ß -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-ß-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS: CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
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OBJECTIVES: Tracheobronchial Talaromyces marneffei (T. marneffei) infections among non-HIV-infected patients are rare. To improve understanding, we analysed the clinical features, immune mechanisms, treatment, and prognosis. METHODS: Data on hospitalized patients with tracheobronchial T. marneffei infections from September 2013 to May 2022 were collected. The clinical and imaging features were analysed. RESULTS: Nineteen patients were enrolled, with a median age of 52 years (45-62 years). The most common symptoms were cough, expectoration, fever, weight loss, and anaemia. The total white blood cell and neutrophil counts, erythrocyte sedimentation rate, C-reactive protein, procalcitonin and globulin were increased, and the serum albumin levels were decreased. Chest CT manifestations included patchy shadows, masses, obstructive atelectasis, cavities, pleural effusion, and hilar and mediastinal lymphadenopathy. The fibreoptic bronchoscopy findings included masses, polyps or nodules with mucosal oedema, hypertrophic bulges, lumen stenosis or obstruction, and purulent secretions. T. marneffei infection was confirmed in 10 patients by positive culture, in five by both culture and metagenomic next-generation sequencing (mNGS), in two by mNGS, in one by culture and pathology and in 1 by histopathology. BALF (15/19, 78.9%) had the highest culture positive rate, followed by sputum (3/19), bronchial mucosa (1/1), lung biopsy (1/2); 36.8% of the patients were coinfected with other pathogens. For induction therapy, 7, 6, 2, and 4 patients received voriconazole, amphotericin B, voriconazole combined with amphotericin B, and fluconazole therapy, respectively, and 26.3% received treatment combined with nebulization and/or administration of amphotericin B under fibreoptic bronchoscopy. Four patients were treated for underlying diseases or coinfection, 31.6% were cured, 42.1% improved, and 26.3% died. CONCLUSIONS: T. marneffei infection is common in the tracheobronchial airway tissue or secretions, and bronchoscopy has important diagnostic and treatment value. Antifungal therapy, including systemic therapy, involves triazoles and amphotericin administration, and aerosol inhalation and administration of amphotericin B under bronchoscopy are important.
T. marneffei infection involving the tracheobronchial region in airway tissue or secretions is high, and bronchoscopy has important value in diagnosing and treating these patientsThe use of triazoles and amphotericin and the aerosol inhalation and instillation of amphotericin B under bronchoscopy are essential to antifungal therapy.
Subject(s)
Amphotericin B , Antifungal Agents , Humans , Middle Aged , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Voriconazole , China/epidemiologyABSTRACT
Objective: To establish a model of emphysema induced by tobacco smoke combined with elastin peptides (EP), explore the biochemical metabolic processes and signal transduction pathways related to emphysema occurrence and development at the transcriptional level, and identify new targets and signaling pathways for emphysema prevention and treatment. Methods: Mice were randomly divided into the air pseudoexposure group (NORMAL group) and the tobacco smoke + EP group (EP group). The differentially expressed genes (DEGs) in lung tissue between the two groups were identified by RNA-seq, and functional annotation and Gene Ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The differential expression of the selected genes were verified using qRTâPCR and immunohistochemistry (IHC). Results: EP group mice showed emphysema-like changes. The expression levels of 1159 genes in the EP group differed significantly (529 up-regulated and 630 down-regulated) from those in the NORMAL group. GO enrichment analysis showed that the DEGs were significantly enriched in the terms immune system, adaptive immune response, and phosphorylation, while KEGG pathway enrichment analysis showed that the DEGs were enriched mainly in the pathways cytokineâcytokine receptor interaction, T-cell receptor signaling pathway, MAPK signaling pathway, Rap1 signaling pathway, endocytosis, chemokine signaling pathway, Th17 cell differentiation, and Th1 and Th2 cell differentiation. The differential expression of the selected DEGs were verified by qRTâPCR and IHC, and the expression trends of these genes were consistent with those identified by RNA-seq. Conclusion: Emphysema may be related to the inflammatory response, immune response, immune regulation, oxidative stress injury, and other biological processes. The Bmp4-Smad-Hoxa5/Acvr2a signaling pathway may be involved in COPD/ emphysema occurrence and development.
Subject(s)
Emphysema , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Tobacco Smoke Pollution , Mice , Animals , Elastin , Pulmonary Emphysema/genetics , Cytokines/genetics , Gene Expression Profiling , Sequence Analysis, RNA , Transcriptome , Computational BiologyABSTRACT
The aim of this study is to find those N7-methylguanosine (m7G) methylation-related regulator genes (m7GMRRGs) which were associated with melanoma prognosis and use them to develop a prognostic prediction model. Clinical information was retrieved online from The Cancer Gene Atlas (TCGA) and the Gene Expression Omnibus (GEO). R software was used to extract m7GMRRGs by differential expression analysis. To create a prognostic risk model, univariate and multivariate Cox regression analyses were employed for the evaluation of the prognostic significance of m7G methylation modifiers. Internal validation using cohort from TCGA (training set) and external validation using cohort from GEO (validation set) of the model were carried out. The model's predictive performance was confirmed by using the Kaplan-Meier, univariate, and multivariate Cox regression, and receiver operating characteristic curve (ROC) by constructing column line plots incorporating clinical factor characteristics. Immune infiltration analyses were performed to assess the immune function of m7GMRRGs. Drug sensitivity analysis was conducted to study chemotherapeutic drug treatment cues. Prognostic models using four m7GMRRGs (EIF4E3, LARP1, NCBP3, and IFIT5) showed good prognostic power in training and validation sets. The area under the curve (AUC) at 1, 3, and 5 years for GEO-melanoma were 0.689, 0.704, and 0.726, respectively. The prediction model could distinctly classify patients with melanoma into different risk subgroups (P < 0.001 for TCGA-melanoma and P < 0.05 for GEO-melanoma). Clinical characteristics were taken into account in Cox regression and AUC analysis, which highlighted that the risk score served as an independent risk factor determining the prognosis of patients with melanoma. Immuno-infiltration analysis showed that m7GMRRGs could potentially regulate CD8+ T cells as well as regulatory T cells (Treg cells). Results of our study indicate a association between m7GMRRGs and melanoma prognosis, and the prognostic prediction model using m7GMRRGs may predict the prognosis of patients with melanoma well. Nevertheless, these results may provide a clue for potential better options of melanoma treatment but need further validation in futural studies.
Subject(s)
CD8-Positive T-Lymphocytes , Melanoma , Humans , Prognosis , Biomarkers , Melanoma/genetics , Genes, RegulatorABSTRACT
Dynamic changes in the microbiome during chronic obstructive pulmonary disease (COPD) exacerbations remain unclear. Using 16S ribosomal DNA and fungal internal transcribed spacer DNA sequencing, we described the composition and changes in the bacterial and fungal microbiota of bronchoalveolar lavage fluid samples from 15 COPD patients and seven non-COPD patients. In patients with COPD, the dominant bacterial phyla were Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. The most abundant fungal phyla were the Ascomycota and Basidiomycota. In terms of the genera of bacteria and fungi, the numbers of Veillonella, Prevotella-7, Haemophilus, and Aspergillus were significantly higher in patients with COPD than in the non-COPD patients. In addition, after the progression of COPD, the relative abundances of the fungal genera Aspergillus, Mortierella, Grifola, Thermoascus, Russula, and Thermomyces and the bacterial genus Proteobacteria increased significantly. Existing analyses have demonstrated changes in the diversity of bacterial and fungal communities, which appear to be related to COPD. Our results demonstrate the potential utility of microbiota as a possible biomarker for disease progression and provide therapeutic targets for COPD.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Bronchoalveolar Lavage Fluid/microbiology , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/analysis , Pulmonary Disease, Chronic Obstructive/microbiology , Bacteria/genetics , Proteobacteria/genetics , Fungi/geneticsABSTRACT
In the recent study, we have developed novel tumor targetable and pH-sensitive PLGA nanoparticles co-loaded with camptothecin (CPT) and metformin (Metf) to simultaneously improve the Type 2 Diabetes Mellitus (T2DM) and malignant breast cancer. To improve the drug loading efficiency, the hydrophobic CPT was conjugated with PLGA polymer by the pH-sensitive hydrazone bonds (hyd). Then, the Metf was physically loaded into the hydrophobicity inner core of CPT-conjugated PLGA nanocomplex to form the dual drugs-loaded nanoparticles (NP/CPT-Metf). Furthermore, on the surface of NP/CPT-Metf was modified with tumor-homing CGKRK peptides to obtain the tumor targetable and pH-sensitive polymer nanoparticles (CNP/CPT-Metf). It was demonstrated that the developed CNP/CPT-Metf displayed sufficient sensitivity to the weak acidic tumor microenvironment. Besides, excellent ability of CNP/CPT-Metf to mediate accumulation of drugs in cells and tumor tissues finally in turn resulted in a signal enhanced anti-tumor effect. Furthermore, it was demonstrated as well that CNP/CPT-Metf was able of significantly alleviating the type 2 diabetes mellitus in diabetic mice. In summary, the developed multifunctional polymer nanoparticles might represent a promising strategy for simultaneously improve the T2DM and treat malignant breast cancer.
Subject(s)
Breast Neoplasms , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Nanoparticles , Animals , Breast Neoplasms/drug therapy , Camptothecin/chemistry , Camptothecin/therapeutic use , Cell Line, Tumor , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Drug Delivery Systems , Female , Humans , Hydrogen-Ion Concentration , Mice , Nanoparticles/chemistry , Polymers , Tumor MicroenvironmentABSTRACT
Background: FAM46C is a common mutated gene in tumours. A comprehensive understanding of the relationship between FAM46C expression and pan-cancer can guide clinical prognosis and broaden the immunotherapeutic targets. Methods: Data from The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were obtained, and gene expression of different tumour types and stages was analysed. Immunohistochemical analysis was performed to detect differences in the FAM46C protein levels in normal and cancerous tissues. The genetic variation of FAM46C was characterised using cBioPortal. The clinical prognostic value of FAM46C and the impact of FAM46C expression levels on the prognosis of patients with different types of cancer were assessed based on Kaplan-Meier and Cox regression analyses. Gene set enrichment analysis (GSEA) was used to analyse the pathways associated with FAM46C. Correlations between FAM46C expression levels and immune infiltration were assessed using the TIMER2 database and CIBERSORT algorithm, and correlations between FAM46C expression and the ESTIMATE, immune and stromal scores were analysed using the ESTIMATE algorithm. In addition, we also analysed the correlation between FAM46C expression and immune activation, suppression genes and immune chemokines. Results: The expression level of FAM46C was correlated with the prognosis of most tumours, and low expression levels often suggested a poor prognosis. FAM46C was positively correlated with the abundance of CD4+ T cells, CD8+ T cells and plasma B lymphocytes in the tumour microenvironment. FAM46C exhibited a strong correlation with immunomodulatory pathways, immunomodulatory factors and immune markers. In addition, high FAM46C expression correlated with tumour mutational burden in acute myeloid leukaemia and microsatellite instability in endometrial cancer. Conclusion: Our study suggests that FAM46C can be a potential prognostic marker for pan-cancer, is closely associated with immune regulation and may be an immune checkpoint to guide future clinical immunotherapy.
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BACKGROUND: The incidence rate of invasive candidiasis is high, its treatment is difficult, and the prognosis is poor. In this study, an immunosuppressive mouse model of invasive Candida albicans (C. albicans) infection was constructed to observe the effects of cinnamaldehyde (CA) on the C. albicans cell wall structure and cell wall (1,3)-ß-D-glucan contents. This study provides a theoretical basis for CA treatment to target invasive C. albicans infection. METHODS: Immunosuppressed mice with invasive C. albicans infection were given an oral dosage of CA (240 mg.kg- 1.d- 1) for 14 days. Then, mouse lung tissue samples were collected for detection of the levels of (1,3)-ß-D-glucan and transmission electron microscopy observations, using fluconazole as a positive control and 2% Tween 80 saline as a negative control. RESULTS: The immunosuppressive mouse model of invasive C. albicans infection was successfully established. The levels of (1,3)-ß-D-glucan in the CA treatment group, fluconazole positive control group, invasive C. albicans infection immunosuppressive mouse model group, and 2% Tween 80 normal saline control group were 86.55 ± 126.73 pg/ml, 1985.13 ± 203.56 pg/ml, 5930.57 ± 398.67 pg/ml and 83.36 ± 26.35 pg/ml, respectively. Statistically, the CA treatment group, fluconazole positive control group and invasive C. albicans infection immunosuppressive mouse model group were compared with each other (P < 0.01) and compared with the 2% Tween 80 saline group (P < 0.01), showing that the differences were very significant. Comparison of the CA treatment group with the fluconazole positive control group (P < 0.05) displayed a difference as well. Electron microscopy showed that CA destroyed the cell wall of C. albicans, where the outer layer of the cell wall fell off and became thinner and the nuclei and organelles dissolved, but the cell membrane remained clear and intact. CONCLUSION: CA destroys the cell wall structure of C. albicans by interfering with the synthesis of (1,3)-ß-D-glucan to kill C. albicans. However, CA does not affect the cell membrane. This study provides a theoretical basis for CA treatment to target invasive C. albicans infection.
Subject(s)
Acrolein/analogs & derivatives , Candidiasis/drug therapy , Glucans/metabolism , Acrolein/pharmacology , Animals , Candida albicans , Cell Wall/drug effects , Disease Models, Animal , Immunocompromised Host , Male , Mice , Mice, Inbred BALB CABSTRACT
INTRODUCTION: Clinical manifestations of hypereosinophilic syndrome (HES) are diverse. This study aimed to summarise these clinical characteristics with asthma-like onset as the first symptom, and compare these characteristics and treatment strategies between idiopathic and parasitic HES. MATERIALS AND METHODS: We retrospectively analysed 36 HES patients with asthma-like symptoms as the first episode, between January 2013 and October 2019. Data of patients with HES of an unknown cause (idiopathic HES) and parasitic infection (parasite HES) were analysed. RESULTS: The idiopathic and parasite HES groups included 16 and 20 patients, respectively, with more males in the parasite HES group (p < .05). Wheezing and dry rales was the most common symptom and signs, with no significant differences in symptoms and signs between the groups. The most often misdiagnosed disease was bronchial asthma. The peripheral blood eosinophil count was significantly increased compared with normal counts in both groups (p > .05). Abnormal pulmonary function is mainly manifested as obstructive ventilatory disorder and mixed ventilatory disorder. Chest computed tomography showed extensive ground-glass exudation, patches, consolidation, nodules, and pleural effusion. Histopathological examination showed eosinophilic infiltration without vasculitis or granuloma. Glucocorticoids had a significant therapeutic effect, and the parasite HES group required combined deworming drugs. The duration of corticosteroids therapy in the idiopathic HES group was significantly longer than that in the parasite HES group (p < .05). The overall prognosis was good, and 81.25% of the patients were clinically cured in the parasite HES group; however, relapse occurred easily in the idiopathic HES group. CONCLUSIONS: Asthma-like symptoms, obstructive ventilatory disorder or positive bronchial dilation test, and poor response to inhaled corticosteroids are not necessarily indicative of refractory asthma; HES should be considered. The clinical characteristics of HES of different aetiologies are similar. Systemic corticosteroid therapy is preferred for idiopathic and parasitic infections. Idiopathic HES is treated with prolonged corticosteroids and relapses easily.Key MessagesAsthma-like symptoms, obstructive ventilatory disorder or positive bronchial dilation tests, and poor responses to inhaled corticosteroids are not necessarily indicative of refractory asthma, and hypereosinophilic syndrome should be considered.The clinical characteristics of hypereosinophilic syndrome of different aetiologies are similar, and systemic glucocorticoid therapy is preferred for both idiopathic and parasitic infections.Idiopathic hypereosinophilic syndrome is treated with prolonged corticosteroids and relapses easily.
Subject(s)
Asthma , Hypereosinophilic Syndrome , Asthma/complications , Asthma/diagnosis , Asthma/drug therapy , Humans , Hypereosinophilic Syndrome/complications , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/drug therapy , Lung , Male , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
We aimed to elucidate the landscape of tumor microenvironment (TME) in triple-negative breast cancer (TNBC). Cohorts from Gene Expression Omnibus database (N = 107) and METABRIC (N = 299) were used as the training set and validation set, respectively. TME was evaluated via single-sample gene set enrichment analysis, and unsupervised clustering was used for cluster identification. Consequently, TNBC was classified into two distinct TME clusters (Cluster 1 and Cluster 2) according to predefined immune-related terms. Cluster 1 was characterized by low immune infiltration with poor prognosis; whereas, Cluster 2 was characterized by high immune infiltration with better survival probability. Further, Cluster 1 had larger tumor volumes, while Cluster 2 had smaller tumor volumes. Finally, a TME signature for prognosis stratification in TNBC was developed and validated. In summary, we comprehensively evaluated the TME of TNBC and constructed a TME signature that correlated with prognosis. Our results provide new insights for the immunotherapy of TNBC.
Subject(s)
Transcriptome , Triple Negative Breast Neoplasms/genetics , Tumor Microenvironment/genetics , Adult , Aged , Cluster Analysis , Female , Gene Expression Profiling , Humans , Lymphocytes, Tumor-Infiltrating , Middle Aged , Neoplasm Staging , Prognosis , Reproducibility of Results , Triple Negative Breast Neoplasms/pathology , Tumor Burden , Unsupervised Machine LearningABSTRACT
OBJECTIVE: To evaluate the effect and safety of cinnamaldehyde on immunosuppressed mice with invasive pulmonary candidiasis. METHODS: An immunosuppressed BALB/c mouse model was established by intraperitoneal administration of cyclophosphamide (200 mg/kg) once daily for 2 days. The immunosuppressed mouse with invasive pulmonary candidiasis model was further established by nasal perfusion of Candida albicans suspension. In the cinnamaldehyde treatment group, immunosuppressed mice with invasive pulmonary candidiasis were orally given cinnamaldehyde 240 mg/(kg·d) for 14 consecutive days. Fluconazole and 0.9% saline were used as the positive and negative controls, respectively. The mice in the cinnamaldehyde safety evaluation group were orally administered cinnamaldehyde 480 mg/(kg·d) for 42 days to observe the safety of the drug. Microscopic identification, fungal culture, histopathological examination, and (1,3)-beta-D-glucans detection were conducted to analyze the effect of cinnamaldehyde on C. albicans. RESULTS: The fungal clearance rate in the cinnamaldehyde treatment group was higher than that in the fluconazole control group (80.00% vs. 56.67%, P<0.05). The level of (1,3)-ß-D-glucan in the cinnamaldehyde treatment group was lower than that in the fluconazole positive control group (1160.62 ±89.65 pg/mL vs. 4285.87 ± 215.62 pg/mL, P<0.05). The survival rate of mice in the cinnamaldehyde safety evaluation group was 100%, and no significant pathological changes of kidney, lung and liver were observed. CONCLUSIONS: Cinnamaldehyde was effective and safe in treating immunosuppressed BALB/c mice with invasive pulmonary candidiasis. It would be a potentially novel drug for anti-candidiasis infection.
Subject(s)
Candidiasis , Acrolein/analogs & derivatives , Animals , Antifungal Agents/therapeutic use , Candida albicans , Candidiasis/drug therapy , Lung , Mice , Mice, Inbred BALB CABSTRACT
BACKGROUND: Henoch-Schonlein purpura (HSP) is a systemic small vessel vasculitis that is mainly caused by IgA1-type immune complex deposition. Advanced oxidation protein products (AOPPs) are specific markers of protein oxidation. OBJECTIVE: To explore the role of AOPPs in the pathogenesis of HSP. METHODS: There are 51 HSP patients who were divided into four subgroups: (i) skin type - 20 cases; (ii) joint type - 8 cases; (iii) abdominal type - 12 cases; (iv) renal type - 11 cases; and 18 healthy volunteers were enrolled as controls. The serum levels of AOPPs and Gd-IgA1 were quantified by an HAA-lectin-based ELISA. The Cosmc mRNA expression in peripheral B lymphocytes was measured by RT-PCR. RESULTS: 1. Advanced oxidation protein products in different subgroups of HSP patients are all higher than the controls, while the renal-type subgroup is the highest and the skin-type subgroup is the lowest. 2. Spearman correlation analysis shows that: (i) AOPPs and Gd-IgA1 in HSP patients are positively correlated; both of them are positively correlated with the disease severity scores; (ii) AOPPs are negatively correlated with the relative expression value (RQ) of Cosmc mRNA. CONCLUSION: Advanced oxidation protein products play an important role in the pathogenesis of HSP, especially in renal-type patients.
Subject(s)
Advanced Oxidation Protein Products/blood , IgA Vasculitis/blood , Immunoglobulin A/metabolism , Molecular Chaperones/genetics , Adolescent , Adult , B-Lymphocytes/metabolism , Biomarkers/blood , Biomarkers/metabolism , Child , Female , Glycosylation , Humans , IgA Vasculitis/diagnosis , IgA Vasculitis/immunology , Immunoglobulin A/blood , Immunoglobulin A/immunology , Male , RNA, Messenger/metabolism , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND: The invasive pulmonary aspergillosis is a kind of high incidence of disease with difficulties in treatment, poor prognosis, and high mortality. OBJECTIVES: The study aimed to reveal the effect of cinnamaldehyde on the fungal cell wall and verify its efficacy on invasive pulmonary aspergillosis on immunosuppressed Institute of Cancer Research mice (ICR mice). METHODS: ICR mice were given cyclophosphamide 200 mg.kg-1. d-1 by intraperitoneal injection for 2 days. On the 4th day, the mice were given 50 µL of Aspergillosis fumigatus spore (107colony form unit CFU/mL) by intranasal injection to establish immunosuppressive animal models with invasive Aspergillosis fumigatus infection. Then the mice in treatment group orally administered cinnamaldehyde for 14 consecutive days, while voriconazole was given to the mice in the positive control group. RESULTS: The clearance rate of pulmonary fungi, cure rate, and reduction of 1,3-ß-D-glucans in treatment group were 80.00%, 80.00%, and 81.00%, respectively while in positive control group they were 67.00%, 60.00%, and 62.00%, respectively. There were significant differences in the results between two groups as mentioned above (P<0.05). Electron microscopy showed that, in treatment group, the cell wall of Aspergillus fumigatus was dissolved and detached and the cell surface was incomplete. There were edema, degeneration, and necrosis in nucleus and organelle, which lead to cellular necrocytosis. The cytomembrane of Aspergillus fumigatus was intact, clear, and complete, whereas the cytomembrane in the positive control group disappeared. The hyphal morphology of Aspergillus fumigatus was deformed, but the cell wall was intact. CONCLUSION: Cinnamaldehyde has a good curative effect in the treatment of invasive pulmonary aspergillus infection in immunodeficient mice. It mainly affects the synthesis of 1,3-ß-D-glucans from the cytoderm of Aspergillus fumigatus but does not affect cell wall. It would potentially be an effective and novel drug for targeted treatment of Aspergillus fumigatus deep infection.
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OBJECTIVE: The traditional decoction method of Dachengqi Tang is that "First boiling Magnolia officinalis and Citrus aurantium with a pipeful of water, taking out five litres from the decoction, removing residues, adding rheum officinale, boiling again, taking out two litres from it, removing residues, adding mirabilite, boiling it with low fire". According to it, residues of M. officinalis and C. aurantium should be removed after decocting. This essay aims to study the content of anthraquinones, in order to proof whether the removal of residues of M. officinalis and C. aurantium is scientific. METHOD: The traditional method was adopted to prepare Dachengqi Tang. Decoction A (original method) was obtained by removing residues of M. officinalis and C. aurantium, whereas decoction B was obtained without removing residues of M. officinalis and C. aurantium. The content of anthraquinones of both methods was determined with HPLC. RESULT: The content of both combined and free anthraquinones in decoction A was higher than that of decoction B. The content of total anthraquinones in residues of decoction A was lower than that of residue B. CONCLUSION: The traditional decoction method of removing residues of M. officinalis and C. aurantium from Dachengqi Tang is scientific, because it improves the dissolution rate of effective ingredients, which provides a theoretical basis for effective substances of the drug.
Subject(s)
Anthraquinones/analysis , Citrus/chemistry , Magnolia/chemistry , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Drug Compounding , Reproducibility of ResultsABSTRACT
The anti-fungus mechanisms and curative effects of cinnamon oil and pogostemon oil complexes towards intestinal Candida infections were investigated. We measured the minimal inhibitory concentration (MIC) values of the complexes against Candida using proportionally-diluted test-tube medium, and examined the evolution of the morphology and structures of Candida albicans using scanning electronic microscopy (SEM) and transmission electronic microscopy (TEM). We found that the average MIC values of the complexes against the fungi were 0.064 mg/mL (cinnamon oil), 0.032 mg/mL (pogostemon oil) for Candida albicans, 0.129 mg/ mL (cinnamon oil), 0.064 mg/mL (pogostemon oil) for Candida tropicalis, and 0.129 mg/mL (cinnamon oil), 0.064 mg/mL (pogostemon oil), for Candida krusei. SEM examination over a 24-48 h period showed that the morphology of Candida albicans cells changed significantly. Irregular hollows appeared on the surfaces, inside organelles were destroyed and the cells burst after treatment. TEM examination over a 48 - 72 h period indicated that the cell walls were damaged, organelles were destroyed and most cytoplasms became empty bubbles. Sixty intestinal Candida-infected patients were treated with a capsule containing cinnamon and pogostemon oil. The curative ratio was 71.67% (43/60), and the improvement ratio was 28.33% (17/ 60), giving a total ratio of 100%. Thus, the cinnamon oil and pogostemon oil complexes had strong anti-fungus effects against Candida albicans, Candida tropicalis, and Candida krusei. They impacted the morphology and sub-micro structures of the fungus within 48 - 72 h, and eventually denatured and killed the cells. The complexes have also shown considerable curative effects to intestinal Candida infections.