ABSTRACT
BACKGROUND: Severe cutaneous adverse drug reactions (SCAR) are life-threatening and contain drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). METHODS: We aimed to evaluate clinical features and prognostic factors for SCAR patients. From January 2010 to April 2022, 209 patients with SCAR (DRESS, n = 46, SJS/TEN, n = 128, AGEP, n = 35) were included in this study. Clinical symptoms, laboratory tests, causative drugs, disease courses, treatments, and outcomes were investigated. RESULTS: Antibiotics ranked first (35.9 %) followed by traditional Chinese medicine (15.8 %) and antiepileptic drugs (14.8 %) among causative drugs of SCAR. One patient (2.2 %) with DRESS and seven patients (5.5 %) with SJS/TEN died in the hospital, while there was no AGEP-related mortality. The multivariate logistic regression analysis showed that high Registry of Severe Cutaneous Adverse Reactions score (OR = 2.340, 95 % CI = 1.192-4.591) and hemoglobin < 100 g/L (OR = 0.126, 95 % CI = 0.016-0.983) were independent risk factors of DRESS. Anemia (OR = 0.191, 95 % CI = 0.037-0.984) and body surface area detached involved at day 1 (OR = 2.749, 95 % CI = 1.115-6.778) were independent risk factors of SJS/TEN for severe acute complications and hospital death (P < 0.05). Lymphocytopenia (OR = 0.004, 95 % CI = 0.000-0.553) was a risk factor of AGEP for acute complications (P = 0.028). CONCLUSION: This study reveals the clinical features and independent prognostic factors for SCAR, which may be helpful in the clinical management for SCAR patients.
Subject(s)
Acute Generalized Exanthematous Pustulosis , Eosinophilia , Stevens-Johnson Syndrome , Humans , Retrospective Studies , Prognosis , Stevens-Johnson Syndrome/diagnosis , Stevens-Johnson Syndrome/etiology , China/epidemiologyABSTRACT
Introduction: Sepsis, an infection with multiorgan dysfunction, is a serious burden on human health. Berberine (BBR), a bioactive component, has a protective effect on sepsis and the effect may be related to gut microbiota. However, studies on the role of BBR with gut microbiota in sepsis are lacking. Therefore, this study investigated the ameliorative effects and the underlying mechanisms of BBR on cecal ligature and puncture (CLP) rats. Methods: This study has observed the effect of BBR on pathological injury, Inflammation, intestinal barrier function, gut microbiota, and metabolite change in CLP rats by Hematoxylin-eosin staining, enzyme-linked immunosorbent assays, flow cytometry, 16S rDNA, and metabolomics analyses. Results: The inhibition effects of BBR treatment on the histological damage of the lung, kidney, and ileum, the interleukin (IL)-1b, IL-6, IL-17A, and monocyte chemokine-1 levels in serum in CLP rats were proved. Also, the BBR inhibited the diamine-oxidase and fluorescein isothiocyanate-dextran 40 levels, suggesting it can improve intestinal barrier function disorders. The cluster of differentiation (CD) 4+, CD8+, and CD25+ Forkhead box protein P3 (Foxp3) + T lymphocytes in splenocytes were up-regulated by BBR, while the IL-17A+CD4+ cell level was decreased. The abundance of gut microbiota in CLP rats was significantly different from that of the sham and BBR treatment rats. The significantly changed metabolites in the serum mainly included carbohydrates, phenols, benzoic acids, alcohols, vitamins et al. Additionally, this study predicted that the biological mechanism of BBR to ameliorate sepsis involves glycolysis-, nucleotide-, and amino acid-related metabolic pathways. Discussion: This study proved the strong correlation between the improvement effect of BBR on sepsis and gut microbiota and analyzed by metabolomics that gut microbiota may improve CLP rats through metabolites, providing a scientific basis for BBR to improve sepsis and a new direction for the study of the biological mechanism.
ABSTRACT
The fermentation of Kadsura angustifolia with an endophytic fungus, Penicillium ochrochloron SWUKD4.1850 yielded five additional undescribed oxygenated terpenoids, kadanguslactones A-E, together with ten known compounds. Their structures were established by the extensive 1D, 2D-NMR, HR-ESI-MS, CD and X-ray crystallography data analysis. Kadanguslactone A is the first example of 1,30-cyclo-3,4; 9,10-disecocycloartanes that combine a five-membered lactone ring A with a cyclopentane ring B consisting of C-1, C-4, C-5, C-10, C-30. Kadanguslactone B was a rare highly oxygenated 18-norschiartane-type bisnortriterpenoid with spirocyclis rings F and G, whereas kadanguslactone C was an uncommon henrischinin-type schitriterpenoid containing a unique 3-one-2-oxabicyclo [3,2,1]-octane motif. The cytotoxicity against HepG2 cell line of all compounds were evaluated. Except nigranoic acid, all other metabolites have been first found in unfermented K. angustifolia, suggesting that main functional ingredients from K. angustifolia may be converted by P. ochrochloron SWUKD4.1850 into highly oxygenated terpenoids. This study provided a fascinating prospective for setting up alternative processing techniques to enhance the functionality and utility of Chinese herbal medicine.
Subject(s)
Kadsura , Penicillium , Fungi , Molecular Structure , Prospective Studies , TerpenesABSTRACT
This study investigated the diversity and host component-transforming activity of endophytic fungi in medicinal plant Kadsura angustifolia. A total of 426 isolates obtained were grouped into 42 taxa belonging to Fungi Imperfecti (65.96%), Ascomycota (27.00%), Zygomycota (1.64%), Basidiomycota (0.47%) and Mycelia Sterilia (4.93%). The abundance, richness, and species composition of endophytic assemblages were significantly dependent on the tissue and the sampling site. Many phytopathogenic species associated with healthy K. angustifolia were found prevalent. Among them, Verticillium dahliae was dominant with 16.43% abundance. From 134 morphospecies selected, 39 showed remarkable biocatalytic activity and were further identified as species belonging to the genera Colletotrichum, Eupenicillium, Fusarium, Hypoxylon, Penicillium, Phomopsis, Trametes, Trichoderma, Umbelopsis, Verticillium and Xylaria on the basis of the sequence analysis of the internal transcribed spacer (ITS1-5.8S-ITS2). The results obtained in this work show that K. angustifolia is an interesting reservoir of pathogenic fungal species, and could be a community model for further ecological and evolutionary studies. Additionally, the converting potency screening of some endophytic fungi from this specific medicinal plant may provide an interesting niche on the search for novel biocatalysts.