Biotransformation of the saponins in Panax notoginseng leaves mediated by gut microbiota from insomniac patients.

Saponins extracted from Panax notoginseng leaves by methanol or water could be orally administrated for insomnia with very low bioavailability, which might be bio-converted by gut microbiota to generate potential bioactive products. Moreover, gut microbiota profiles from insomniac patients are very different from healthy subjects. We aimed to compare the metabolic characteristics and profiles of the two saponins extract by incubation with gut microbiota from insomniac patients. The ginsenosides, notoginsenosides, and metabolites were identified and relatively quantified by high-performance liquid chromatography-tandem mass spectrometry. Gut microbiota was profiled by 16S ribosomal RNA gene sequencing. The results showed that saponins were very different between methanol or water extract groups, which were metabolized by gut microbiota to generate similar yields. The main metabolites included ginsenoside Rd, ginsenoside F2 , ginsenoside C-Mc or ginsenoside C-Y, ginsenoside C-Mx, ginsenoside compound K, and protopanaxadiol in both groups, while gypenoside XVII, notoginsenoside Fe, ginsenoside Rd2 , and notoginsenoside Fd were the intermediates in the methanol group. Moreover, the microbial, Faecalibacterium prausnitzi, could bio-convert the saponins to obtain the corresponding metabolites. Our study implied that saponins extracted from P. notoginseng leaves by methanol or water could be used for insomniac patients due to gut microbiota biotransformation.

Stem cell therapy as a promising strategy in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that affects newborns, particularly preterm infants, and is associated with high morbidity and mortality. No effective therapeutic strategies to decrease the incidence and severity of NEC have been developed to date. Stem cell therapy has been explored and even applied in various diseases, including gastrointestinal disorders. Animal studies on stem cell therapy have made great progress, and the anti-inflammatory, anti-apoptotic, and intestinal barrier enhancing effects of stem cells may be protective against NEC clinically. In this review, we discuss the therapeutic mechanisms through which stem cells may function in the treatment of NEC.

[Evaluation of mid-term follow-up after Salter innominate osteotomy in developmental dysplasia of the hip].

OBJECTIVES: To evaluate the mid-term outcome after Salter innominate osteotomy in developmental dysplasia of the hip (DDH), and to observe the developmental characteristics of the hip after operation and the relationships between the mid-term outcome and radiographic parameters as well as age at operation. METHODS: : Forty-four patients with 61 treated hips were selected. The patients were treated with Salter innominate osteotomy and followed-up for at least three years with intact serial radiographs. Radiographs taken before operation, 6 weeks, 1 year and 2 - 3 years after operation and in the latest follow-up were selected. Acetabular index (AI), Sharp acetabular angle (SAA) and center-edge angle of Wiberg (CEA) were measured and Severin classification was done according to radiographs taken in the latest follow-up. RESULTS: The average correction of AI was 14° postoperatively. The acetabulum remodels best at 2-3 years after operation when the average AI became very close to normal. In the latest follow-up the SAA was 41° which could be regarded as normal. Postoperative CEA was on average 23° which increased to 25° 2-3 years later. In the latest follow-up, the average CEA was 26°. The ratio of excellent and good outcomes (Severin I, II) was 84%, while the ratio of moderate and poor outcomes (Severin III, IV, V, VI) was 16%. Age at operation had a negative effect on outcomes. Although 70% patients operated after age 6 had satisfactory outcomes. The Severin I, II group showed no difference in AI from III, IV, V, VI group 6 weeks after operation, but the AI of the former obviously improved 2-3 years after operation while that of the latter deteriorated. Significant difference in SAA and the CEA could be observed in the latest follow-up. CONCLUSIONS: Salter innominate osteotomy focuses on normalizing the abnormal acetabular direction in DDH children as well as stimulating the remodeling of the acetabulum, which provides a satisfactory middle-term outcome. The acetabulum remodels rapidly during the first three years after operation when AI and CEA develops into normal. Interference should be adopted if these changes have not appeared in the first three years.

AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease.

Angiotensin II, which is the main effector of the renin­angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription-quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis-related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS-induced body weight loss and colonic damage. Furthermore, T helper 1-mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan-treated mice. Losartan also increased the B-cell lymphoma 2 (Bcl2)/Bcl-2-associated X protein (Bax) ratio and suppressed caspase-3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS-induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl-2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase-3.

Vitamin D/VDR signaling attenuates lipopolysaccharide­induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier.

Vitamin D and its receptor have a protective effect on epithelial barriers in various tissues. Low levels of vitamin D are associated with numerous pulmonary diseases, including acute lung injury (ALI) and acute respiratory distress syndrome. The present study investigated whether the vitamin D/vitamin D receptor (VDR) pathway may ameliorate lipopolysaccharide (LPS)­induced ALI through maintaining the integrity of the alveolar epithelial barrier. This was investigated by exposing wild­type (WT) and VDR knockout C57BL/6J mice to LPS, then comparing the healthy and LPS­treated mice lungs and bronchoalveolar lavage fluid (BALF). More specifically, lung histology, mRNA levels of proinflammatory cytokines and chemokines, and protein expression levels of tight junction proteins were determined. In addition, a vitamin D analog (paricalcitol) was administered to WT mice in order to investigate the effect of vitamin D on the alveolar epithelial barrier following exposure to LPS. VDR knockout mice exhibited severe lung injuries (P<0.001), increased alveolar permeability [demonstrated by a higher wet­dry ratio of lung weight (P<0.05), greater expression levels of BALF protein (P<0.001) and fluorescein isothiocyanate­conjugated 4 kDa dextran (P<0.001) leakage into the alveolar space], elevated proinflammatory cytokine and chemokine mRNA levels, as demonstrated by reverse transcription­quantitative polymerase chain reaction (P<0.05), and decreased protein and mRNA expression levels of occludin (P<0.01) and zonula occludens­1 (ZO­1; P<0.01) compared with WT mice. Paricalcitol treatment partially inhibited these pathological changes in WT mice by maintaining the mRNA and protein expression levels of occludin (P<0.01) and ZO­1 (P<0.05). A lack of VDRs in the pulmonary epithelial barrier appeared to compromise its defense, leading to more severe LPS­induced lung injury. Furthermore, vitamin D treatment alleviated LPS­induced lung injury and preserved alveolar barrier function. Therefore vitamin D treatment may present as a potential therapeutic strategy in ALI and acute respiratory distress syndrome.

Vitamin D/VDR signaling pathway ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis by inhibiting intestinal epithelial apoptosis.

Increasing epidemiological data have suggested a link between vitamin D deficiency and the incidence of inflammatory bowel disease (IBD). In the present study, we confirmed that vitamin D deficiency, as well as the decreased local expression of vitamin D receptor (VDR), was prevalent in an IBD cohort. The excessive apoptosis of intestinal epithelial cells (IECs) partly accounts for the development of colonic inflammation and eventually results in IBD. Based on the established inhibitory effects of the vitamin D/VDR pathway on IEC apoptosis, we treated mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis with paricalcitol, a vitamin D analog, in order to investigate the mechanisms responsible for the inhibitory effects of the vitamin D/VDR pathway. We observed that following treatment with vitamin D, the mice presented with only minor bodyweight loss, and the mice also showed improved histological scores and decreased intestinal epithelial permeability compared with the vehicle-treated group. The colonic mRNA expression of inflammatory cytokines and chemokines was markedly suppressed, indicating less severe colitis in the vitamin D-treated mice. Subsequently, we investigated p53 upregulated modulator of apoptosis (PUMA) and p53, two major independent pathways of apoptosis, as well as caspase-3. We found that the vitamin D-treated mice had lower expression levels of caspase-3 than the vehicle-treated mice. PUMA expression showed the same tendency; however, the p53 protein level was not altered. The present study indicates that vitamin D attenuates the development of TNBS-induced colitis by inhibiting the apoptosis of IECs. The mechanisms involved include the downregulation of PUMA expression. Our data provide experimental support for the clinical trials of vitamin D intervention in patients with IBD.