Salvianolic Acids: Potential Source of Natural Drugs for the Treatment of Fibrosis Disease and Cancer

Salvianolic acids, the most effective and abundant compounds extracted from Salvia miltiorrhiza (Danshen), are well known for its good anti-oxidative activity. Danshen has been extensively used as a traditional medicine to treat cardiovascular-related diseases in China and other Asian countries for hundreds of years. Recently, more and more studies have demonstrated that salvianolic acids also have a good effect on the alleviation of fibrosis disease and the treatment of cancer. In vivo and in vitro experiments have demonstrated that salvianolic acids can modulate signal transduction within fibroblasts and cancer cells. It is discovered that the cancer treatment of salvianolic acids is not only because salvianolic acids promote the apoptosis of cancer cells, but also due to the inhibition of cancer-associated epithelial-mesenchymal transition processes. In this article, we review a variety of studies focusing on the comprehensive roles of salvianolic acids in the treatment of fibrosis disease and cancer. These perspectives on the therapeutic potential of salvianolic acids highlight the importance of these compounds, which could be the novel and attractive drugs for fibrosis disease and cancer

Circulating endothelial progenitor cells decrease in infants with bronchopulmonary dysplasia and increase after inhaled nitric oxide.

BACKGROUND: Impairment of endothelial progenitor cells (EPCs) has been shown to contribute to the development of bronchopulmonary dysplasia (BPD). In the current study, the relationship between EPC changes of after birth and the development of BPD was investigated, and the effects of inhaled nitric oxide (iNO) on EPCs were evaluated. METHODS: Sixty infants with a gestational age of less than 32 weeks and a birth weight of less than 1500 g were studied. NO was administered to infants who were receiving mechanical ventilation or CPAP for at least 2 days between the ages of 7 and 21 days. EPC level was determined by flow cytometry at birth, 7, 21 and 28 days of age and 36 weeks' postmenstrual age (PMA), before and after the iNO treatment. Plasma concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and granulocyte-macrophage colony-stimulating factor were determined via immunochemical assay. RESULTS: Twenty-five neonates developed BPD, 35 neonates survived and did not develop BPD. EPC level was decreased on day 7 and 21 in infants who later developed BPD compared with infants that did not develop BPD. From birth to 21 days of age, BPD infants had a persistently lower VEGF concentration compared with non-BPD infants. No difference was found between the two groups at day 28 or 36 weeks PMA. In infants that later developed BPD, iNO raised the KDR(+)CD133(+) and CD34(+)KDR(+)CD133(+) EPC numbers along with increasing the level of plasma VEGF. CONCLUSION: EPC level was reduced at 7 days of age in infants with BPD, and iNO increased the EPC number along with increasing the level of VEGF. Further studies are needed to elucidate the mechanism leading to the decrease of EPCs in infants with BPD and to investigate the role of iNO treatment in the prevention of BPD

MicroRNAs as Mediators of Adipose Thermogenesis and Potential Therapeutic Targets for Obesity

Obesity is a growing health problem worldwide, associated with an increased risk of multiple chronic diseases. The thermogenic activity of brown adipose tissue (BAT) correlates with leanness in adults. Understanding the mechanisms behind BAT activation and the process of white fat “browning” has important implications for developing new treatments to combat obesity. MicroRNAs (miRNAs) are small transcriptional regulators that control gene expression in various tissues, including adipose tissue. Recent studies show that miRNAs are involved in adipogenesis and adipose tissue thermogenesis. In this review, we discuss recent advances in the role of miRNAs in adipocyte thermogenesis and obesity. The potential for miRNA-based therapies for obesity and recommendations for future research are highlighted, which may help provide new targets for treating obesity and obesity-related diseases

A rule-based algorithm for automatic bond type perception

Abstract Assigning bond orders is a necessary and essential step for characterizing a chemical structure correctly in force field based simulations. Several methods have been developed to do this. They all have advantages but with limitations too. Here, an automatic algorithm for assigning chemical connectivity and bond order regardless of hydrogen for organic molecules is provided, and only three dimensional coordinates and element identities are needed for our algorithm. The algorithm uses hard rules, length rules and conjugation rules to fix the structures. The hard rules determine bond orders based on the basic chemical rules; the length rules determine bond order by the length between two atoms based on a set of predefined values for different bond types; the conjugation rules determine bond orders by using the length information derived from the previous rule, the bond angles and some small structural patterns. The algorithm is extensively evaluated in three datasets, and achieves good accuracy of predictions for all the datasets. Finally, the limitation and future improvement of the algorithm are discussed.</p

The percentages of cell subsets in circulating blood at different time points in infants with and without BPD.

<p>Data are presented as medians with 25–75% quartiles. MNC = mononuclear cells.</p

Inhaled NO Contributes to Lung Repair in Piglets with Acute Respiratory Distress Syndrome via Increasing Circulating Endothelial Progenitor Cells

Background: Nitric oxide (NO) plays an important role in mobilization of endothelial progenitor cells (EPCs). We hypothesized that inhaled NO (iNO) would induce EPC mobilization and therefore promote lung repair in acute respiratory distress syndrome (ARDS). Methodology/Principal Findings: Healthy piglets were randomized into four groups (n = 6): Control (Con; mechanical ventilation only); ARDS (established by oleic acid infusion and mechanical ventilation); ARDS plus granulocyte-colony stimulating factor (G-CSF; 10 mg/kg/d subcutaneously); ARDS plus NO inhalation (iNO; 10 ppm). EPCs and mobilizing cytokines were assayed at different time points (baseline, 0, 24, 72 and 168 h) and injury reparation was assessed at 168 h. Compared to the Con group, the levels of EPCs were increased in bone marrow but not in blood in the ARDS group at 24 h. Compared to the ARDS group, inhaled NO induced a rapid elevation in the number of CD34 + KDR +, KDR + CD133 + and CD34 + KDR + CD133 + EPCs in blood (21636454 vs. 10946416, 13026413 vs. 4296244, 11406494 vs. 4536273 cells/ml, respectively, P,0.05), and a reduction in the percentage of KDR + CD133 + cells in bone marrow. Lung CD34, CD133, VEGF, VEGF receptor 2, endothelial NO synthase mRNA, and VEGF and VEGF receptor 2 protein expression levels were augmented in the iNO group, but not in the G-CSF group, compared to ARDS. Furthermore, iNO treatment reduced vascular permeability, increased pulmonary vessel density, and alleviated pulmonary edema and inflammation compared to ARD

Effect of Dietary Salt Intake on Risk of Gastric Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies

Aim: The effect of dietary salt intake on the risk of gastric cancer is not clear. A meta-analysis was performed to estimate the association between dietary salt intake and the risk of gastric cancer. Methods: Three major databases were searched to retrieve case-control studies published in English before 1 July 2022. Random effects model analysis was used to obtain the pooled odds ratios (ORs) and 95% confidence intervals (CIs) of the association between dietary salt intake and risk of gastric cancer. Subgroup analyses were used to identify possible sources of heterogeneity. Results: Thirty-eight case-control studies were included in this meta-analysis (total population: n = 37,225). The pooled ORs showed a significantly positive association between high salt intake and gastric cancer compared with low salt intake (OR = 1.55, 95% CI (1.45, 1.64); p &lt; 0.001). In subgroup meta-analysis for geographic region, estimation method for dietary salt intake and the source of controls, this association was not changed. Conclusion: Higher dietary salt intake increased the risk of gastric cancer. This study has implications for the prevention of gastric cancer

Comparison of chicoric acid, and its metabolites caffeic acid and caftaric acid: In vitro protection of biological macromolecules and inflammatory responses in BV2 microglial cells

Chicoric acid (CA), a natural phenolic acid, has been used as a nutraceutical food ingredient due to its powerful antioxidant, anti-HIV and anti-diabetic bioactivities. CA could be partly metabolized into caffeic acid (CFA) and caftaric acid (CTA) on cytochrome P450s in rat liver microsomes. To compare the protective effects of CA and its metabolites on biomolecules and inflammatory responses, oxidative damage induced by free radicals in vitro and microglial inflammation triggered by lipopolysaccharide in BV2 cells were constructed. Results showed that CA, CTA and CFA all significantly inhibited protein degradation and carbonylation induced by hydroxyl radicals and alcoxyl radicals, and suppressed hemin/nitrite/H2O2 triggered-nitration. Moreover, CA, CTA and CFA all exerted remarkable inhibition capacities on linoleic acid and soybean lecithin liposomes peroxidation in a dose-dependent manner, and restrained the oxidation of herring sperm DNA, as well as the breakage of pBR322 plasmid DNA. Furthermore, CA and its metabolites suppressed lipopolysaccharide-induced decline of BV2 cell viability and the production of NO and ROS. However, bioactivities of CA were significantly stronger than those of its metabolites within a certain concentration range. This study provides scientific basis for the application of CA and its metabolites as nutrition and natural antioxidants

EPC level in infants with different severity of BPD at day 7.

<p>(A) CD34⁺KDR⁺ cells. (B) KDR⁺CD133⁺ cells. (C) CD34⁺KDR⁺CD133⁺ cells. The level of EPCs was significantly lower in infants with severe BPD compared to infants with mild BPD. Values in boxplot are expressed as median, 25th, and 75th percentiles. MNC =  mononuclear cells. *<i>P</i><0.05.</p