Gut microbiota trajectory in ß-thalassemia major children who underwent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The gut microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) changes, leading to complications such as acute graft-versus-host disease (GVHD). This study aimed to evaluate the human microbiota composition before and after HSCT in ß-thalassemia major (ß-TM) children. METHOD: Twenty-two ß-TM children who received allo-HSCT between December 2018 and March 2020 were enrolled. They were followed up for more than 100 days after HSCT, and their gut microbiota information and disease data were recorded at five-time points. RESULTS: The dominant bacteria were Bacteroidetes and Firmicutes at the phylum level and Lachnospiraceae at the family level before and after HSCT. In the differential analysis, Ruminococcaceae constantly decreased after HSCT. Besides, Rothia mucilaginosa was the most abundant 2 months after HSCT compared to before it. Additionally, GVHD patients presented decreased levels of Bacteroidetes compared to those without GVHD. Moreover, Blautia levels significantly decreased in critically ill GVHD patients. CONCLUSION: The gut microbiota of the 22 ß-TM children showed a clear trend of destruction and reconstruction within 100 days after HSCT. The extra-oral infections and inflammations of Rothia mucilaginosa, a Gram-positive bacterium of the normal oropharyngeal tract microbiota, might play an important role in the recovery process of HSCT. Finally, decreased Bacteroidetes levels were associated with GVHD onset.

Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate.

Jatrorrhizine, a protoberberine alkaloid derived from Coptis chinensis, is currently under investigation as a natural gastric prokinetic drug candidate. In vitro and in vivo studies were conducted to characterize its pharmacokinetics and metabolism. After intravenous administration, the plasma concentration kinetics and major metabolites in rats were investigated. The metabolic kinetics, key cytochrome P450 enzymes and UDP-glucuronosyltransferase isoforms (UGTs) of jatrorrhizine were studied in rat liver microsomes (RLMs). After intravenous administration, plasma jatrorrhizine concentrations showed a biphasic decline, dose-independent clearance and half-life of terminal elimination phase, and a relatively large distribution volume. The metabolic pathway for the conversion of jatrorrhizine was important for its elimination. In addition, the demethylated and glucuronidated products were found to be the major metabolites in rats. The enzyme kinetics for both demethylation and glucuronidation were fitted to the hyperbolic Michaelis-Menten equation in RLMs. CYP3A1/2 and CYP2D2 were mainly responsible for demethylation, and UGT 1A1 and 1A3 were responsible for glucuronidation in RLMs. The metabolic properties of jatrorrhizine suggest multiple metabolic pathways. These results will contribute to promote further research and development of jatrorrhizine.

Arylnaphthalene lignan glycosides and other constituents from Phyllanthus reticulatus.

Two new arylnaphthalene lignan glycosides, named reticulatusides A (1) and B (2), together with eight known compounds were isolated from the 95% EtOH extract of the whole plant of Phyllanthus reticulatus. The structures of the new compounds were elucidated by spectroscopic methods.

Prognostic Observational Analysis of BMI, Leptin, and Adiponectin in Children With Acute Lymphocytic Leukemia Undergoing Remission-Induction Chemotherapy.

Background: The survival rate of children and adolescents with acute lymphoblastic leukemia (ALL) has progressively improved. However, ALL survivors often have adverse effects after treatment, such as an increased risk of obesity. Obesity has been associated with reduced survival. Objective: We investigated the relationship between obesity, adipocytokine levels, and ALL short-term outcomes. Methods: Weight and height were measured, and body mass index (BMI) was calculated at patient diagnosis and discharge. Leptin and Adiponectin levels and Minimal Residual Disease (MRD) were measured before therapy, at days 19 of remission-induction therapy, and at the end of remission-induction therapy (days 46). The relationship between BMI, adipocytokine levels, and MRD was then determined. Results: Compared to the normal BMI group, children with an abnormal increase in BMI had an increase in MRD at day 19 and 46 (P = 0.04 and P = 0.008), and showed a positive correlation (P = 0.014). In addition, we found a positive correlation between weight, hip circumference at diagnosis and at day 19, and MRD at day 46. Both BMI and fat concentric distribution affected the outcome of ALL children. A higher BMI was also associated with a significant increase in Leptin levels at diagnosis. Leptin resistance should be considered in ALL children with high BMI. Conclusion: BMI affects the outcome of ALL patients. Early interventions such as regular weight, height monitoring, and dietary assessments should be preferably initiated during remission-induction chemotherapy.

Anthropometric parameters of obesity can be alternative biomarkers for the potential cardiac dysfunction in obese children.

Childhood obesity, as one of the potential risk factors of cardiovascular diseases, is closely associated with the incidence of cardiovascular disease at a younger age and has become a public health concern worldwide. However, its potential effects on the cardiovascular system have still remained elusive. In this study, we systematically evaluated the cardiovascular characteristics of 79 obese children and 161 normal weight children in Guangzhou (China) using the potential biomarkers for cardiovascular disease. Compared with normal weight children, obese children not only exhibited significantly higher levels of creatine kinase (CK), lactate dehydrogenase (LHD), soluble fms-like tyrosine kinase-1 (s-Flt-1), high-sensitivity C-reactive protein (hs-CRP), and uric acid (UA) (p = 0.0062, 0.0012, 0.0013, 0.0225, and <0.0001, respectively) but also significantly higher diastolic blood pressure (p = 0.0074) and the heart rate (p = 0.0049) were found in obese children. Of 79 obese children, cardiac functions of 40 cases were further assessed by color Doppler echocardiography. The results showed that there were significant differences between the obesity group and the healthy weight group in terms of interventricular septal wall thickness at end-diastolic (IVSd), the left ventricular posterior wall thickness at end-diastolic (LVPWD), and aortic annulus (AO) (p < 0.0001, 0.0003, and p < 0.0001, respectively). Besides, the left and/or right ventricular functions were declined in 52.4% of obese children. Correlation analysis revealed that the anthropometric parameters of obesity were not only significantly correlated with a blood lipid profile but also exhibited a more significant correlation with most of the parameters of cardiac dysfunction than a blood lipid profile. Therefore, our study indicated that obese children in Guangzhou suffered from functional damages related to cardiovascular events, which were characterized by cardiac dysfunction, and the anthropometric parameters of obesity could be economically alternative biomarkers for monitoring of cardiac dysfunction in obese children.

Chemical constituents from the leaves of Aglaia perviridis.

A new cinnamic acid-derived bisamide 1 and a new oplopanone-type sesquiterpenoid diglycoside 2, together with 11 known compounds, were isolated from the 95% ethanolic extract of the leaves of Aglaia perviridis. Their structures were elucidated by chemical and spectroscopic methods.

In vitro actions on human cancer cells and the liquid chromatography-mass spectrometry/mass spectrometry fingerprint of phytochemicals in rice protein isolate.

Rice protein isolate (RPI) has been reported to reduce the incidence of 7,12-dimethylbenz[a]anthracene-induced mammary tumors in rats. To determine the potential role of phytochemicals associated with the RPI, we studied in vitro antitumor activities of an ether fraction from RPI using human tumor cell lines, including two human breast carcinoma cell lines (MDA-MB-453 and MCF-7) and two myeloma cell lines (RPMI-8226 and IM-9). Concentration-dependent antiproliferative effects of the ether fraction were observed in all cell lines using the standard 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Fraction-induced apoptosis (P < 0.05) was detected in all cell lines, and this was associated with the induction of proapoptotic bax protein and cdk inhibitors (p21) and the suppression of cdk4 and cyclin D1 activity. Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) with both positive and negative modes was used to analyze the phytochemicals in the ether fraction from RPI. Fifty-seven phytochemicals were identified or characterized by their diagnostic fragmentation patterns and direct comparison with the authentic standards on the basis of electrospray ionization-MS/MS data. The major components bound to RPI were lysoglycerophospholipids, fatty acids, and fatty acid 3-[2-(2,3-dihydroxy-propoxycarbonyl)-2-hydroxy-ethoxy]-2-hydroxy-propyl esters.

Cytotoxic hydroxylated triterpene alcohol ferulates from rice bran.

Three hydroxylated triterpene alcohol ferulates, (24S)-cycloart-25-ene-3 beta,24-diol-3 beta-trans-ferulate (1), (24R)-cycloart-25-ene-3 beta,24-diol-3 beta-trans-ferulate (2), and cycloart-23Z-ene-3 beta,25-diol-3 beta-trans-ferulate (3), along with known compounds cycloartenol trans-ferulate (4) and 24-methylenecycloartanol trans-ferulate (5) were isolated from rice bran. Their structures were elucidated by means of chemical and spectroscopic analysis. Compounds 2-5 showed moderate cytotoxicity against MCF-7 cells.