Effect of traditional Chinese medicine in attenuating chronic kidney disease and its complications by regulating gut microbiota-derived metabolite trimethylamine N-oxide: a review / 中国中药杂志

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.

Protective Effect and Mechanism of Aqueous Extract of Perillae Folium on Adriamycin-induced Oxidative Injury in HK-2 Cell / 中国实验方剂学杂志

Objective: To investigate the protective effect of Perillae Folium with aqueous extract (PFAE) on some key factors of Adriamycin (ADR)-induced oxidative injury in human renal tubular epithelial cells(HK-2), including the survival rate, oxidative injury indexes and cell apoptosis,in order to define the underlying mechanism. Method: A model of ADR-induced HK-2 cells oxidative injury was established in vitro, then cell viability was detected by cell counting kit-8 (CCK-8) after intervention with positive reference N-acetylcysteine (NAC) or PFAE (5,15,45 g·L-1) at different concentrations. According to the morphological changes under microscopy, the optimum concentration of PFAE was screened out for the follow-up experiments. Then, the experiments were divided into six groups:blank group, ADR (0.05 g·L-1) group, PFAE (15 g·L-1) group, ADR+PFAE (0.05+15) g·L-1 group, NAC (0.81 g·L-1) group, and ADR+NAC (0.05+81) g·L-1 group. After that, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity(TAC) were measured in the cell homogenate after 24 h administration. The level of reactive oxygen species (ROS) was detected by 2',7'-dichloroflurescin diacetate (DCFH-DA) fluorescence probe. Flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to monitor the cell apoptosis. Western blot was used to observed the expressions of mitochondrial apoptosis-associated proteins, like B lymphocyte tumor-2 gene (Bcl-2), Bcl-2 related X protein (Bax), cysteine aspartate protease-9 (Caspase-9), cysteine aspartate protease-3 (Caspase-3) and poly ADP-ribose polymerase (PARP), as well as their shear bodies. In addition, the phosphorylation protein expressions of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signaling transduction pathway were detected by Western blot. Result: Compared with blank group, ADR group showed a decreased cell viability (PPPPPPPP-1. The ATC and SOD levels were increased in ADR+PFAE group and ADR+NAC group (PPConclusion: PFAE could alleviate the oxidative injury of HK-2 cells induced by ADR, and have an antioxidant effect, which inhibited cell apoptosis through mitochondrial apoptotic pathway and ERK/p38 MAPK signaling pathway.

Comparison of total hip and knee joint replacement in patients with rheumatoid arthritis and osteoarthritis: a nationwide, population-based study

<p><b>INTRODUCTION</b>Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) may require total hip replacement (THR) or total knee replacement (TKR). The present study aimed to compare the demographic characteristics and medical costs of RA and OA patients from Taiwan who underwent either THR or TKR.</p><p><b>METHODS</b>The medical records of patients who had undergone THR or TKR from 1 January 1996 to 31 December 2010 were obtained from the Taiwan National Health Insurance Research Database (NHIRD). In all, we found 49 and 146 RA patients who received THR and TKR, respectively, and 1,191 and 6,574 OA patients who received THR and TKR, respectively. The gender, age, Charlson comorbidity index (CCI), hospital grade, age at registration in the catastrophic illness dataset, and medical utilisation costs of the different groups were compared.</p><p><b>RESULTS</b>There were statistically significant differences in age, CCI score, drug costs and surgery costs between RA and OA patients. Joint replacement incidence was lower in RA patients than in OA patients, and among patients who underwent THR, total medical costs incurred were higher for RA patients than OA patients. RA patients who underwent THR incurred a significantly greater total medical utilisation cost in the outpatient department (3 months before surgery and 12 months after surgery) than OA patients who underwent THR.</p><p><b>CONCLUSION</b>Analysis of Taiwan NHIRD with regard to patients who had undergone either THR or TKR indicated that RA patients were younger than OA patients, and that significantly more medical resources were used for RA patients before, during and after hospitalisation for these procedures.</p>

Altered regional homogeneity in spontaneous cluster headache attacks: a resting-state functional magnetic resonance imaging study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Functional neuroimaging study has opened an avenue for exploring the pathophysiology of cluster headache (CH). The aim of our study was to assess the changes in brain activity in CH patients by the regional homogeneity method using resting-state functional magnetic resonance imaging technique.</p><p><b>METHODS</b>The functional magnetic resonance imaging scans were obtained for 12 male CH patients with spontaneous right-sided headache attacks during "in attack" and "out of attack" periods and 12 age- and sex-matched normal controls. The data were analyzed to detect the altered brain activity by the regional homogeneity method using statistical parametric mapping software.</p><p><b>RESULTS</b>Altered regional homogeneity was detected in the anterior cingulate cortex, the posterior cingulate cortex, the prefrontal cortex, insular cortex, and other brain regions involved in pain processing and modulation among different groups.</p><p><b>CONCLUSION</b>It is referred that these brain regions with altered regional homogeneity might be related to the pain processing and modulation of CH.</p>

A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.</p><p><b>METHODS</b>Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Our results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest.</p><p><b>CONCLUSIONS</b>In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.</p>

Differential generation of hydrogen peroxide upon exposure to zinc and cadmium in the hyperaccumulating plant species (Sedum alfredii Hance) / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Sedum alfredii Hance has been identified as zinc (Zn) and cadmium (Cd) co-hyperaccumulator. In this paper the relationships of Zn or Cd hyperaccumulation to the generation and the role of H2O2 in Sedum alfredii H. were examined. The results show that Zn and Cd contents in the shoots of Sedum alfredii H. treated with 1000 micromol/L Zn2+ and/or 200 micromol/L Cd2+ increased linearly within 15 d. Contents of total S, glutathione (GSH) and H2O2 in shoots also increased within 15 d, and then decreased. Total S and GSH contents in shoots were higher under Cd2+ treatment than under Zn2+ treatment. However, reverse trends of H2O2 content in shoots were obtained, in which much higher H2O2 content was observed in Zn2+-treated shoots than in Cd2+-treated shoots. Similarly, the microscopic imaging of H2O2 accumulation in leaves using H2O2 probe technique showed that much higher H2O2 accumulation was observed in the Zn2+-treated leaf than in the Cd2+-treated one. These results suggest that there are different responses in the generation of H2O2 upon exposure to Zn2+ and Cd2+ for the hyperaccumulator Sedum alfredii H. And this is the first report that the generation of H2O2 may play an important role in Zn hyperaccumulation in the leaves. Our results also imply that GSH may play an important role in the detoxification of dissociated Zn/Cd and the generation of H2O2.