Cytotoxic Effects of Oleanane-type Saponins from Lysimachia laxa.

Phytochemical investigation of the methanol extract of the aerial parts of Lysimachia laxa led to the isolation of four new oleanane-type saponins, lysimosides A-D (1-4) and one known compound, lysimachigenoside B (5). Their structures were elucidated using a combination of HR-ESI-MS, 1D and 2D-NMR spectral data, chemical methods, and comparison with previous literature. The cytotoxic activity of these compounds was evaluated against human lung cancer (A-549) and human breast cancer (MCF-7) cell lines. All compounds exhibited cytotoxic activity against A-549 and MCF-7 cell lines with IC50 values ranging from 6.1 to 16.0 µM, comparable to the positive control, mitoxantrone. Interestingly, oleanane-type saponins with an acetyl group (2-4) exhibited increased cytotoxic activities compared to those without an acetyl group (1).

Cyclosporine A-induced systemic metabolic perturbations in rats: A comprehensive metabolome analysis.

A better understanding of cyclosporine A (CsA)-induced nephro- and hepatotoxicity at the molecular level is necessary for safe and effective use. Utilizing a sophisticated study design, this study explored metabolic alterations after long-term CsA treatment in vivo. Rats were exposed to CsA with 4, 10, and 25 mg/kg for 4 weeks and then sacrificed to obtain liver, kidney, urine, and serum for untargeted metabolomics analysis. Differential network analysis was conducted to explore the biological relevance of metabolites significantly altered by toxicity-induced disturbance. Dose-dependent toxicity was observed in all biospecimens. The toxic effects were characterized by alterations of metabolites related to energy metabolism and cellular membrane composition, which could lead to the cholestasis-induced accumulation of bile acids in the tissues. The unfavorable impacts were also demonstrated in the serum and urine. Intriguingly, phenylacetylglycine was increased in the kidney, urine, and serum treated with high doses versus controls. Differential correlation network analysis revealed the strong correlations of deoxycytidine and guanosine with other metabolites in the network, which highlighted the influence of repeated CsA exposure on DNA synthesis. Overall, prolonged CsA administration had system-level dose-dependent effects on the metabolome in treated rats, suggesting the need for careful usage and dose adjustment.

Successful Treatment of Carbamazepine-Induced Toxic Epidermal Necrolysis With Clinical Gastrointestinal Involvement: A Case Report.

Background: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare and life-threatening disease of the skin and mucosal surfaces. Although gastrointestinal manifestations in adults are potential prognostic factors for disease severity, there are limited data on such cases and their standard management in the pediatric population. Case Presentation: We herein report the case of an 8-year-old girl with a 1-year history of epilepsy, who presented with bilateral conjunctivitis and progressively widespread bullous, and pruritic eruption based on erythematous skin after administration of carbamazepine. A diagnosis of carbamazepine-induced TEN was made, and the drug was immediately discontinued. The result of genetic screening showed that the patient was positive for the HLA-B*15:02 allele. Then, her condition got worse by developing gastrointestinal involvement, including hematemesis and severe watery bloody diarrhea. A combination of the intravenous immunoglobulin and the appropriate dose of systemic steroids have contributed to a favorable outcome in this case. Multidisciplinary care of mucocutaneous involvement, supplemental nutrition, and fluid replacement was also critically warranted. This report aims to contribute to the current literature on TEN-related gastrointestinal manifestations in pediatrics and highlights the need for further investigations in determining the optimal treatment in such cases. Conclusion: In conclusion, we reported the successful treatment of TEN-related gastrointestinal manifestations in a pediatric patient, which should be critically considered in patients with SJS/TEN. Since it may significantly contribute to the poor prognosis of the illness, further investigations in determining standard management in such cases are necessary.

Novel mutations in unrelated Vietnamese patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder (PID) due to genetic defects in the NADPH oxidase of phagocytes. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. The patients require life-long treatment with prophylactic antibiotics, antifungals, or hematopoietic stem cell transplantation (HSCT) therapy. Early, accurate diagnosis will contribute to the life-prolonging of patients with CGD. This study's aim is to identify the mutation related to the disease. CASE PRESENTATION: Six patients from different Vietnamese families were collected for genetic analysis at Allergy, Immunology, and Rheumatology Department, Vietnam National Hospital Pediatrics. They were diagnosed with CGD by flow cytometry test with the conversion of dihydrorhodamine (DHR) 123 to rhodamine 123. METHODS: We performed whole exome sequencing (WES) as a tool for detecting novel mutations. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen 2, Mutation Taster, and MaxEntScan. RESULTS: In this study, five mutations were found in six unrelated patients with CGD from different Vietnamese families. Three novel pathogenic mutations were detected including one mutation (c.45+2 T>G) in the CYBB gene and two mutations (c.187_188insA and c.289G>C) in the NCF2 gene. CONCLUSIONS: Our results of CGD-related mutations contribute to the general understanding of the etiology of the disease and emphasize that WES sequencing can be used as a tool to help to diagnose carriers as well as assist in genetic counseling and prenatal screening.

A Potent Antioxidant Sesquiterpene, Abelsaginol, from Abelmoschus sagittifolius: Experimental and Theoretical Insights.

The sesquiterpenoid compound abelsaginol (AS) was successfully isolated from Abelmoschus sagittifolius for the first time. The compound was identified using NMR and MS data. The antioxidant activity of AS was also evaluated both theoretically and experimentally. AS was found to be a weak HOO• radical scavenger in organic solvents such as pentyl ethanoate and dimethyl sulfoxide (k overall = ∼ 102 M-1 s-1), in a good agreement with the results of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. However, AS exhibited good HOO• antiradical activity in water at pH 7.40 (k overall = 9.00 × 106 M-1 s-1) through the single-electron transfer mechanism of the anion state. Further calculations also demonstrated that AS could exert good to moderate activity against CH3O•, CH3OO•, CCl3OO•, NO2, and SO4 •- radicals, with k f values from 4.00 × 103 to 1.52 × 107 M-1 s-1. However, AS exerted much lower activity against HO•, CCl3O•, NO, O2 •-, and N3 • radicals under the studied conditions. In general, the activity of AS in water at pH 7.40 is higher than that of Trolox or butylated hydroxytoluene, which are common reference antioxidants. Thus, in an aqueous physiological milieu, AS is a promising natural antioxidant.