Citrus aurantium

Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n=47) and control group (CG, received 20 mg placebo daily, n=48). After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group (P>0.01). The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability

IκB Kinase Inhibitor VII Modulates Sepsis-Induced Excessive Inflammation and Cardiac Dysfunction in 5/6 Nephrectomized Mice

Background. Chronic kidney disease condition requires regular dialysis; the patients have greater risk of sepsis and have high mortality rate compared to general people with sepsis. The adverse cardiac condition leads to mortality in subjects with sepsis. In the present work, we studied the consequences of chronic kidney damage by 5/6 nephrectomy on cardiac function in mice induced with sepsis and the mechanism involved. Methods. We used C57BL/6 mice and subjected them to 5/6 nephrectomy; after induction of chronic kidney damage, they were subjected to sepsis by either LPS treatment or by cecal ligation and puncture (CLP) method. The cardiac function test was done by echocardiography. Protein expression was done by western blot analysis. Results. The 5/6 nephrectomized mice showed significant increase in blood creatinine and urea levels compared to sham-operated mice; the mice also showed decreased ejection fraction and increased levels of phosphorylated IkBα and nuclear translocation of the NF-κB and inducible nitric oxide synthase (iNOS). When subjected to CLP and LPS treatment, the 5/6 nephrectomized mice augmented cardiac abnormalities and lung inflammation and increased plasma levels of TNF-α, IL-1, IL-12, and IL-18. Also, we evidenced increased levels of p-IKKα/β and Ikβα, NF-κβ, and iNOS. Treatment of IKK inhibitor VII in 5/6 nephrectomized mice after LPS administration or CLP attenuated these effects. Conclusion. Chronic kidney disease could lead to abnormal cardiac function caused by sepsis in mice; this may be due to increased expression of NF-κβ and iNOS in cardiac tissues

TMT-Based Proteomic Analysis of Plasma from Children with Rolandic Epilepsy

Rolandic epilepsy is one of the most common epileptic syndromes in childhood. We used TMT-based proteomics and bioinformatics analysis to identify the differentially expressed proteins in plasma of children with Rolandic epilepsy. Our aim was to provide a molecular basis for exploring possible mechanisms underlying the pathogenesis of epilepsy. Subjects were divided into two groups (five in each): patients with Rolandic epilepsy as cases and patients with migraine as controls. Total proteins were extracted and quantitatively labeled with TMT, then analyzed using liquid chromatography mass spectrometry. Bioinformatics analysis was used to identify the hub genes. A total of 752 proteins were identified, of which 670 contained quantitative proteins. 217 differentially expressed proteins were identified, 46 of which were only upregulated in more than two groups and 111 of which were only downregulated in more than two groups. Bioinformatics analysis revealed top 10 hub genes in the up- and downregulated groups, respectively. Our study demonstrates that some differentially expressed proteins are associated with epilepsy. Activation of acute-phase or innate immune response and complement and fibrinogen systems and repression of glycolysis, lipoprotein metabolism, and antioxidant activity may play a role in the development of epilepsy

Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway

Abstract Background Mesenchymal stem cells (MSCs) are increasingly being applied as a therapy for liver fibrosis. Exosomes possess similar functions to their parent cells; however, they are safe and effective cell-free reagents with controllable and predictable outcomes. In this study, we investigated the therapeutic potential and underlying molecular mechanism for human bone mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) in the treatment of liver fibrosis. Methods We established an 8-week CCl4-induced rat liver fibrosis model, after which, we administered hBM-MSCs-Ex in vivo for 4 weeks. The resulting histopathology, liver function, and inflammatory cytokines were analyzed. In addition, we investigated the anti-fibrotic mechanism of hBM-MSCs-Ex in hepatic stellate cells (HSCs) and liver fibrosis tissue, by western blotting for the expression of Wnt/β-catenin signaling pathway-related genes. Results In vivo administration of hBM-MSCs-Ex effectively alleviated liver fibrosis, including a reduction in collagen accumulation, enhanced liver functionality, inhibition of inflammation, and increased hepatocyte regeneration. Moreover, based on measurement of the collagen area, Ishak fibrosis score, MDA levels, IL-1, and IL-6, the therapeutic effect of hBM-MSCs-Ex against liver fibrosis was significantly greater than that of hBM-MSCs. In addition, we found that hBM-MSCs-Ex inhibited the expression of Wnt/β-catenin pathway components (PPARγ, Wnt3a, Wnt10b, β-catenin, WISP1, Cyclin D1), α-SMA, and Collagen I, in both HSCs and liver fibrosis tissue. Conclusions These results suggest that hBM-MSCs-Ex treatment could ameliorate CCl4-induced liver fibrosis via inhibition of HSC activation through the Wnt/β-catenin pathway

Association between low ambient temperature during pregnancy and adverse birth outcomes: A systematic review and meta-analysis

Abstract. Background:. Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. Methods:. Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. Results:. A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04–1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03–1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99–5.38). Conclusions:. Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. Registration:. No. CRD42021259776 at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/)