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After a high-fat and high-sugar diet, the duodenal mucosa of rodents proliferate and trigger the signal of insulin resistance, which may be the cause of type 2 diabetes (T2D). In response to this phenomenon, researchers have designed the duodenal mucosal resurfacing (DMR) procedure, mainly through the hydrothermal ablation procedure, to restore the normal mucosal surface, thereby correcting this abnormal metabolic signal. This article aims to understand the changes in duodenum before and after the onset or treatment of T2D, and the potential mechanisms of DMR procedure.A literature search of PubMed and Web of Science was conducted using appropriate keywords.Both animal and clinical studies have shown that the villus thickness, intestinal cells, glucose transporters, enteric nerves, and gut microbiota and their metabolites in the duodenum undergo corresponding changes before and after the onset or treatment of T2D. These changes may be related to the pathogenesis of T2D. DMR procedure may produce beneficial glycemic and hepatic metabolic effects by regulating these changes.The duodenum is an important metabolic signaling center, and limiting nutrient exposure to this critical region will have powerful metabolic benefits. The DMR procedure may regulate glycemic and hepatic parameters through various mechanisms, which needs to be further confirmed by a large number of animal and clinical studies.

Aims To evaluate the efficacy of hyperoside and the role of TGF-β1/miR-200b/VEGF pathway in treating diabetic retinopathy (DR). Methods (1) Retinal endothelial cells (RECs) were cultured in the normal-glucose group (NG), high-glucose group (HG), mannitol group, high glucose + low-concentration hyperoside group, high glucose + high-concentration hyperoside group, normal glucose + miR-200b inhibitor group (NG + MI), normal glucose + normal control group (NG + NC), high glucose + miR-200b mimic group (HG + MM), and high glucose + normal control group (HG + NC). The viability, migration and tube formation of RECs, and the expressions of TGF-β1, miR-200b and VEGF in each group were detected and compared. (2) Eight Sprague Dawley (SD) rats were used in the normal control group, and 32 SD rats established DR models were randomly divided into the four groups for DR group (DR), DR + low-dose hyperoside group, DR + high-dose hyperoside group, and DR + Calcium Dobesilate group. The tissue pathology and vasculopathy of rat retina, and the expressions of TGF-β1, miR-200b, and VEGF of retinal tissues in different group were tested and compared. Results (1) Excessive proliferation, migration and tube formation of RECs were induced by high glucose. The expressions of TGF-β1 and VEGF in HG were markedly up-regulated, but miR-200b levels were obviously down-regulated. However, hyperoside could significantly reverse the expressions of TGF-β1, VEGF and miR-200b; and inhibit high-glucose-induced over-proliferation of RECs dose-dependently. RECs viability and VEGF level were much higher in NG + MI than for NG but lower in HG + MM than for HG, while miR-200b level was substantially lower in NG + MI than for NG but higher in HG + MM than for HG. (2) The retinal pathological changes and vasculopathy in DR rats were more serious compared with normal rats. TGF-β1 and VEGF levels in DR rats retina were markedly up-regulated, while miR-200b levels were obviously down-regulated. However, hyperoside could notably reverse the expressions of TGF-β1, VEGF, and miR-200b in DR rat retina and alleviate retinal tissue injury and vascular lesions of DR rats dose-dependently. Conclusion Hyperoside could treat DR by regulating TGF-β1/miR-200b/VEGF pathway.

AIMS/INTRODUCTION In this paper, we focused on exploring the diagnostic and predictive clinical utility of ankle-brachial index (ABI) in combination with feet electrochemical skin conductance (FESC) for peripheral artery disease (PAD) in Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS Overall, 183 Chinese T2DM patients were enrolled in this study. The patients were classified into three groups: Group 1 comprised of uncomplicated type 2 diabetics (n = 36), Group 2 consisted of patients with diabetic peripheral neuropathy (n = 103) whereas Group 3 patients displayed peripheral artery disease (n = 44). All patients underwent Sudoscan test using a Sudoscan (Paris, France) and ABI assessment. RESULTS Multivariate logistic regression models revealed that FESC was an independent risk factor of developing PAD in patients with type 2 diabetes. The AUC for diagnostic, positive predictive and negative predictive value of ABI in combination with FESC for PAD were 0.907, 0.733 and 0.920, respectively. The specificity and sensitivity of ABI in combination with FESC for PAD were 0.914 and 0.750, respectively. CONCLUSIONS Ankle-brachial index in combination with FESC can accurately be used in early diagnosis of PAD.

Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that serves as a potent mediator of cell proliferation, differentiation and apoptosis by binding to S1P receptors (S1PRs). S1P signalling is involved in the pathogenesis of numerous types of disease, including cancer. To the best of our knowledge, however, little is known about the expression patterns of S1PRs and their role in human colorectal cancer (CRC) cell migration and invasion. The aim of the present study was to investigate the role of S1P signalling in the metastasis of colon cancer cells and the expression of S1PRs in patients with CRC. The protein and mRNA expression levels of S1PRs and sphingosine kinases (SPHKs) in 55 patients with CRC were detected by western blotting (WB), immunohistochemical (IHC) analysis and reverse transcription-quantitative PCR. The levels of S1P in serum from patients and healthy individuals were quantified by ELISA. S1PRs antagonists JTE013, FTY720 and S1PR2-small interfering (si)RNA were used to determine the role of S1PR2 in human CRC LOVO and SW480 cell lines. Migration and invasion assays were performed for functional analysis. The levels of S1P in serum were significantly increased in patients with CRC compared with healthy individuals. The relative mRNA expression levels of S1PR2 were significantly downregulated in tumour compared with normal tissue, whereas S1PR1 and SPHK1 were upregulated. WB showed that 58% (32/55 cases) of patients presented downregulated S1PR2 protein expression. IHC analysis indicated that expression of S1PR2 was lower in tumour than in normal tissue in 65.5% (36/55 cases) of patients. Exogenous addition of S1P promoted migration and invasion in the different cell types. S1P stimulated the migration and invasion of SW480 cells. The inhibition of S1PR2 by JTE013 or S1PR2-siRNA significantly promoted the migration and invasion of SW480 cells, while FTY720 reversed these effects. The present study indicated that expression levels of S1PRs, particularly S1PR2, were associated with migration and invasion of CRC cells. The present findings revealed a novel mechanism by which S1P inhibited tumour cell migration and invasion via a S1PR2-dependent pathway, suggesting that S1PR2 may be a therapeutic target for treatment of colon cancer.

Histamine is a major peripheral inflammatory mediator and a neurotransmitter in the central nervous system. We have reported that histamine induces microglia activation and releases proinflammatory factors in primary cultured microglia. Whether histamine has similar effects in vivo is unknown. In the present study, we aimed to investigate the role of histamine and its receptors in the release of inflammatory mediators and activation of microglia in rat brain. We site-directed injected histamine, histamine receptor agonists or histamine receptor antagonists in the rat lateral ventricle using stereotaxic techniques. Flow cytometry was employed to determine histamine receptor expression in rat microglia. Microglia activation was assessed by Iba1 immunohistochemistry. The levels of tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-10 (IL-10) were measured with commercial enzyme-linked immunosorbent assay (ELISA) kits, TNF-α, IL-1β and IL-10 mRNA expressions were determined with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). We found that all four types of histamine receptors were expressed in rat brain microglia. Histamine was able to induce microglia activation and subsequent production of the inflammatory factors TNF-α, IL-1β and IL-10, and these effects were partially abolished by H1R and H4R antagonists. However, H2R and H3R antagonists significantly increased production of TNF-α and IL-1β, and decreased IL-10 levels. The H1R or H4R agonists stimulated the production of TNF-α and IL-1β, while the H2R or H3R agonists increased IL-10 release. Our results demonstrate that histamine induces microglia activation and the release of both proinflammatory and anti-inflammatory factors in rat brain, thus contributing to the development of inflammation in the brain. Graphical Abstract Histamine induces microglia activation and the release of both proinflammatory (TNF-α and IL-1β) and anti-inflammatory factors (IL-10) in rat brain, thus contributing to the development of inflammation in the brain.

Inflammation plays an essential role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Berberine (BBR), an isoquinoline alkaloid isolated from Chinese medicinal herbs, has been widely used to treat various diseases, including liver diseases for hundreds of years. The previous studies have shown that BBR inhibits high fat-diet-induced steatosis and inflammation in rodent models of NAFLD. However, the underlying molecular mechanisms remain unclear. This study is aimed to identify the potential mechanisms by which BBR inhibits free fatty acid (FFA) and LPS-induced inflammatory response in mouse macrophages and hepatocytes. Mouse RAW264.7 macrophages and primary mouse hepatocytes were treated with palmitic acid (PA) or LPS or both with or without BBR (0–10 μM) for different periods (0–24 h). The mRNA and protein levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1) and ER stress genes (CHOP, ATF4, XBP-1) were detected by real-time RT-PCR, Western blot and ELISA, respectively. The results indicated that BBR significantly inhibited PA and LPS-induced activation of ER stress and expression of proinflammatory cytokines in macrophages and hepatocytes. PA/LPS-mediated activation of ERK1/2 was inhibited by BBR in a dose-dependent manner. In summary, BBR inhibits PA/LPS-induced inflammatory responses through modulating ER stress-mediated ERK1/2 activation in macrophages and hepatocytes.

Histamine is a major peripheral inflammatory mediator and a neurotransmitter in the central nervous system. We have reported that histamine induces microglia activation and releases proinflammatory factors in primary cultured microglia. Whether histamine has similar effects in vivo is unknown. In the present study, we aimed to investigate the role of histamine and its receptors in the release of inflammatory mediators and activation of microglia in rat brain. We site-directed injected histamine, histamine receptor agonists or histamine receptor antagonists in the rat lateral ventricle using stereotaxic techniques. Flow cytometry was employed to determine histamine receptor expression in rat microglia. Microglia activation was assessed by Iba1 immunohistochemistry. The levels of tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-10 (IL-10) were measured with commercial enzyme-linked immunosorbent assay (ELISA) kits, TNF-α, IL-1β and IL-10 mRNA expressions were determined with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). We found that all four types of histamine receptors were expressed in rat brain microglia. Histamine was able to induce microglia activation and subsequent production of the inflammatory factors TNF-α, IL-1β and IL-10, and these effects were partially abolished by H

Hepatocellular carcinoma (HCC) is an aggressive malignancy. In HCC, mitogen-activated protein kinase (MAPK) signaling is overactivated. The MAPK kinase (MEK) inhibitor trametinib has been approved to treat several types of advanced cancers with a BRAF mutation. Herein, we examined whether trametinib has efficacy against HCC. The effects of trametinib on cell viability, proliferation and tumor growth were assessed in HCC-derived cell lines and mouse xenograft models. Western blot analysis and immunohistochemistry were used to identify key regulators critical for HHC cell proliferation and tumor growth. We found that trametinib dose-dependently inhibited the viability and proliferation of HCC cells. We also found that a strong suppression of MEK by trametinib downregulated the pro-survival protein MYC, but upregulated the pro-apoptotic protein BIM. This dual differential regulation of MYC and BIM was found to be accompanied by upregulation of a MYC-targeted cyclin dependent kinase inhibitor, p27kip1 (p27), and an apoptosis marker, cleaved poly (ADP ribose) polymerase 1 (PARP), indicating a concurrent modulation of cell cycle- and apoptosis-related pathways. Importantly, we found that MYC overexpression did not block increased BIM in trametinib-treated HCC cells, indicating that MAPK signaling independently regulates MYC and BIM. Finally, we found that trametinib in vivo inhibited HepG2 xenograft tumor growth and attenuated tumor invasion into surrounding tissues. Consistent with the in vitro findings, MYC expression was found to be reduced, while p27 expression was found to be elevated, and BIM expression and cleaved PARP levels were found to be increased in trametinib-treated xenograft tumors. Collectively, our data indicate that trametinib exhibits efficacy in treating HCC cells via distinct regulation of the MYC and BIM pathways. As such, targeting MEK to block MAPK signaling with trametinib may provide novel treatment opportunities for HCC.

Insulin-like growth factor-1 (IGF-1) -induced epithelial-mesenchymal transition (EMT) plays a key role in the metastasis and drug resistance of non-small cell lung cancer (NSCLC). Sphingosine kinase-1 (SphK1) is also involved in EMT of NSCLC. However, the interaction between SphK1 and IGF-1 in the EMT of NSCLC is largely unknown. To clarify this issue, we examined the involvement of SphK1 in IGF-1-induced EMT using human lung cancer cell line A549, and its paclitaxel-resistant subline. Cell viability was evaluated by cell counting kit-8 assay; Migratory ability was examined using scratch wound healing test; Protein expression levels of SphK1, vimentin, fibronectin, N-cadherin and E-cadherin were detected by western blot analysis, respectively. The results showed that, IGF-1 treatment of A549 cells stimulated the expression of SphK1, the activation of ERK and AKT, the cell migration, and the expression of EMT hallmark proteins, while inhibition of SphK1 by its specific inhibitor SKI-II suppressed all the above changes and increased the sensitivity of A549 cells to paclitaxel. Our data demonstrate that SphK1 acts as a downstream effector of IGF-1 and plays a critical role in IGF-1-induced EMT, cell migration and paclitaxel resistance of A549 cells, suggesting that SphK1 might be a potential therapeutic target for NSCLC.

Objective The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. Conclusions XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.

Long-term macrolides are increasingly being prescribed for stable bronchiectasis. This meta-analysis assessed the clinical effect of this treatment in bronchiectasis. A systematic review and meta-analysis were carried out. All randomized, controlled trials (RCT) comparing long-term macrolides with placebo and/or usual medical care, with outcome measures relating to efficacy and safety were selected. Nine RCT recruiting 530 patients were included. Compared with placebo and/or usual medical care, long-term macrolides significantly reduced the risk of the exacerbations (number of participants with exacerbations (relative risk = 0.70, 95% confidence interval (CI) 0.60–0.82, P

Background: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. The current study examined the effect of HIF-2α, an oxygen-sensitive heterodimeric transcription factor, on hypoxia-induced dysregulation of lipid metabolism in HepG2 cells. Methods: Studies were conducted in C57BL/6 male mice and human HepG2 cells under hypoxic conditions, transfected with HIF-2α-targeted shRNA. The mRNA and protein expressions of key genes relevant to lipid metabolism were determined via RT-qPCR and western blot, respectively. Intracellular lipid accumulation was determined by Nile red, filipin staining and quantitative assay kits. Results: HIF-2α protein was quantified in both HepG2 cells and C57BL/6 mice under hypoxic conditions. Intracellular lipid accumulation and increased lipid levels induced by hypoxia were significantly reduced by silence of HIF-2α expression, associated with reversed expression of ABCA1 and ADRP, key genes in involved cholesterol excretion and fatty acid uptake respectively. However, HIF-2α had no effect on enzymatic activity and expression of key genes involved in fatty acid β-oxidation or cholesterol metabolism. Conclusion: Inhibition of HIF-2α protein reversed lipid metabolism dysregulation induced by acute hypoxia in HepG2 cells, which suggested that HIF-2α signaling may be relevant to oxygen-dependent lipid homeostasis in the liver.

The aim of this study was to examine the association between polymorphisms in the interleukin-3 and -13 (IL-3 and IL-13) genes and rheumatoid arthritis (RA). In this hospital-based case-control study, we analyzed the IL-3 rs2073506 G/A, IL-3 rs40401 C/T, and IL-13 rs1800925 C/T polymorphisms in 615 RA patients and 839 controls from a Chinese Han population. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism scanTM kit. Our results indicated that the IL-3 rs2073506 G/A, IL-3 rs40401 C/T, and IL-13 rs1800925 C/T polymorphisms were not associated with RA. However, stratification analyses suggested that the IL-13 rs1800925 CT and CT/CC genotypes increased the risk of RA in patients with erythrocyte sedimentation rate (ESR)

Bile acids have been shown to be important regulatory molecules for cells in the liver and gastrointestinal tract. They can activate various cell signaling pathways including extracellular regulated kinase (ERK)1/2 and protein kinase B (AKT) as well as the G-protein-coupled receptor (GPCR) membrane-type bile acid receptor (TGR5/M-BAR). Activation of the ERK1/2 and AKT signaling pathways by conjugated bile acids has been reported to be sensitive to pertussis toxin (PTX) and dominant-negative Gα(i) in primary rodent hepatocytes. However, the GPCRs responsible for activation of these pathways have not been identified. Screening GPCRs in the lipid-activated phylogenetic family (expressed in HEK293 cells) identified sphingosine-1-phosphate receptor 2 (S1P(2) ) as being activated by taurocholate (TCA). TCA, taurodeoxycholic acid (TDCA), tauroursodeoxycholic acid (TUDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and S1P-induced activation of ERK1/2 and AKT were significantly inhibited by JTE-013, a S1P(2) antagonist, in primary rat hepatocytes. JTE-013 significantly inhibited hepatic ERK1/2 and AKT activation as well as short heterodimeric partner (SHP) mRNA induction by TCA in the chronic bile fistula rat. Knockdown of the expression of S1P(2) by a recombinant lentivirus encoding S1P(2) shRNA markedly inhibited the activation of ERK1/2 and AKT by TCA and S1P in rat primary hepatocytes. Primary hepatocytes prepared from S1P(2) knock out (S1P(2) (-/-) ) mice were significantly blunted in the activation of the ERK1/2 and AKT pathways by TCA. Structural modeling of the S1P receptors indicated that only S1P(2) can accommodate TCA binding. In summary, all these data support the hypothesis that conjugated bile acids activate the ERK1/2 and AKT signaling pathways primarily through S1P(2) in primary rodent hepatocytes.

Hypoxia inducible factor 1α (HIF-1α) is highly expressed and is implicated in the progression of esophageal squamous cell carcinoma. To investigate the potential mechanism by which HIF-1α contributes to the progression of esophageal squamous cell carcinoma, here we established stable esophageal carcinoma cell lines Eca-109 and TE- 13 in which HIF-1α was depleted by shRNA mediated gene silencing. In additon, we used specific inhibitor YC-1 to inhibit HIF-1α expression. Our in vitro studies demonstrated that shRNA or chemical mediated inhibition of HIF-1α led to reduced proliferation and increased apoptosis of esophageal carcinoma cells, as well as the downregulatuion of HIF-1α targets VEGF, MMP2 and BCL2. Furthermore, we employed xenograft nude mice model to validate the in vitro findings and proved that depletion of HIF-1α suppressed the tumorigenicity of esophageal carcinoma cells in vivo. In conclusion, our results provide new insight into the potential role of HIF-1α in esophageal squamous cell carcinoma and open up the possibility of inhibiting HIF-1α for targeted therapy of esophageal squamous cell carcinoma.

Background and objective: Tiotropium is the only long-acting inhaled anticholinergic bronchodilator currently available in China, but information about its clinical effect in this population is limited. This meta-analysis assessed the efficacy and safety of tiotropium in Chinese patients with stable COPD. Methods: An electronic search of the literature was undertaken to identify randomized controlled trials (RCTs) of tiotropium in Chinese patients, which were then assessed for inclusion in a meta-analysis. The efficacy and safety of tiotropium was compared with placebo and ipratropium, using the outcomes of FEV1, FEV1%, symptoms, frequency of exacerbations, adverse events and safety. Results: Eleven RCTs recruiting 1006 patients were included in the meta-analysis. Compared with both placebo and ipratropium, tiotropium significantly improved FEV1[weighted mean difference (WMD) = 304 mL, 95% CI 271–337], FEV1% (WMD = 8.35%, 95% CI 5.40–11.31) and symptoms [relative risk (RR) = 2.00, 95% CI 1.61–2.49]. Tiotropium significantly reduced the risk of exacerbations (RR = 0.07, 95% CI 0.01–0.54) compared with placebo, and there was a non-significant reduction in the risk of exacerbations compared with ipratropium (RR = 0.70, 95% CI 0.13–3.75). Tiotropium was well tolerated with a similar safety profile to placebo and ipratropium (RR = 1.16, 95% CI 0.76–1.77, P = 0.49). Conclusions: Tiotropium improved pulmonary function and symptoms, reduced exacerbations and was well tolerated and safe. On the basis of its efficacy and safety profile, tiotropium appears to be a reasonable first-line choice for the management of Chinese patients with stable COPD. Additional long-term RCTs are required to further evaluate the efficacy and safety of tiotropium.

Brain inflammation has a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells are the "first responder" in the injury rather than microglia. Functional aspects of mast cell-microglia interactions remain poorly understood. Our results demonstrated that site-directed injection of the "mast cell degranulator" compound 48/80 (C48/80) in the hypothalamus induced mast cell degranulation, microglial activation, and inflammatory factor production, which initiated the acute brain inflammatory response. "Mast cell stabilizer" disodium cromoglycate (cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced microglial activation, inhibition of MAPK and AKT pathways, and repression of protein expression of histamine receptor 1 (H1R), histamine receptor 4 (H4R), protease-activated receptor 2 (PAR2), and toll-like receptor 4 (TLR4) in microglia. We also demonstrated that C48/80 had no effect on microglial activation in mast cell-deficient KitW-sh/W-sh mice. These results implicate that activated brain mast cells trigger microglial activation and stabilization of mast cell inhibits microglial activation-induced central nervous system (CNS) inflammation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.

Long-term macrolides are increasingly being prescribed for stable bronchiectasis. This meta-analysis assessed the clinical effect of this treatment in bronchiectasis. A systematic review and meta-analysis were carried out. All randomized, controlled trials (RCT) comparing long-term macrolides with placebo and/or usual medical care, with outcome measures relating to efficacy and safety were selected. Nine RCT recruiting 530 patients were included. Compared with placebo and/or usual medical care, long-term macrolides significantly reduced the risk of the exacerbations (number of participants with exacerbations (relative risk = 0.70, 95% confidence interval (CI) 0.60-0.82, P 0.00001); average exacerbations per participant (weighted mean difference = -1.01, 95% CI -1.35 to -0.67, P 0.00001)), the St George's Respiratory Questionnaire total scores (weighted mean difference = -5.39 95% CI -9.89 to -0.88, P = 0.02), dyspnoea scale (weighted mean difference = -0.31 95% CI -0.42 to -0.20, P 0.00001), 24-h sputum volume (P 0.00001), and attenuated the decline of forced expiratory volume in 1 s (weighted mean difference 0.02 L, 95% CI 0.00-0.04, P = 0.01). Eradication of pathogens (P = 0.06), overall rate of adverse events (P = 0.61), and emergence of new pathogens (P = 0.61) were not elevated, while gastrointestinal events increased significantly with macrolides (P = 0.0001). Macrolide resistance increased, but a meta-analysis was not possible due to the diversity of parameters. Long-term use of macrolides appears to be a treatment option for stable bronchiectasis. The results of this review justify further investigation about adding this intervention to the treatment regimens of bronchiectasis.

Introduction: Colorectal cancers (CRC) express Angiogenin (ANG), Galectin-3 (Gal-3) and Activin A (Act-A). The binding of ANG to actin on endothelial cell promote EC migration and angiogenesis. Cellular Gal-3 levels associated with cancer cell invasion, angiogenesis and tumor progression. Act-A act via binding to trans membrane receptors and support cancer cell migration. Blood levels of ANG, Gal-3 and Act-A in colorectal cancer (CRC) have not been well studied. This study's purpose was to measure preoperative (PreOp) plasma ANG, Gal-3 and Act-A levels in CRC and benign pathology (BP) patients (pts.) and to assess the diagnostic efficacy of these proteins alone and together. Method: CRC or BP pts having bowel resection for whom PreOp plasma was available (from IRB approved tissue bank) were studied. Plasma ANG (ng/ml), Gal-3 and Act-A (pg/ml) levels were analyzed in duplicate via ELISA (results: median + 95%CI). Intergroup levels were compared by the Mann-Whitney test (significant;p

Background. Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. According to a recent report, rats studied 3 weeks after 5/6 nephrectomy and fed a high-protein diet exhibited increased activities of hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase (Cyp7a1), despite normal corresponding mRNA levels. Design and Methods. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the bile acid synthesizing enzyme Cyp7a1 and the bile acid transporters, Ntcp, Bsep, Mrp3, Ost-alpha and OST-beta. Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy) or to the sham-operated, placebo-treated normal control group. They were allowed free access to regular rat chow and were analyzed 8 weeks after surgery. Results obtained in CRF rats were compared to those obtained in rats that had undergone uninephrectomy (UNX). Results. The CRF group exhibited significantly increased plasma cholesterol and bile acid concentrations. Hepatic Cyp7a1 mRNA, and protein levels were almost identical in the two groups. Hepatic Mrp3, Ostα and Ost-β expression was increased at both the mRNA and protein levels, suggesting increased basolateral efflux of bile acids into basolateral blood. However, no such changes in bile acid transporter expression were observed in kidney. In UNX rats, similar changes in plasma bile acid levels and in the expression of bile acid transporters were found. We hypothesize, that the increase in plasma bile acids is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.