An eight-week home-based inspiratory muscle training is feasible and effective in improving both inspiratory and expiratory muscle strength, but has no effect on respiratory function and quality of life in patients with bronchiectasis.

BackgroundDiabetes is a proinflammatory state. Fibrosis of the renal glomerulus is the most common cause of end-stage renal disease. Glomerulosclerosis is caused by the accumulation of extracellular matrix (ECM) proteins in the mesangial interstitial space. Mesangial cells are unique stromal cells in the renal glomerulus that form the vascular pole of the renal corpuscle along with the mesangial matrix. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells that rapidly expand to regulate host immunity during inflammation, infection, and cancer. High concentrations of granulocyte–macrophage colony-stimulating factor (GM-CSF) alone or in combination with other molecules represent the most common ex-vivo protocol for differentiating MDSCs from bone marrow or from peripheral blood mononuclear cells. In this study, we analyzed and characterized the functions of MDSCs under the influence of mouse mesangial cells (MMCs) in a hyperglycemic environment and investigated whether cytokine-induced MDSCs ameliorated renal glomerulosclerosis in diabetic mice.MethodsCytokine-induced MDSCs were propagated from bone marrow cells cultured with mouse recombinant GM-CSF, IL-6, and IL-1β. Diabetic mice were induced with streptozotocin (STZ) and maintained at a blood glucose concentration exceeding 350 mg/dl. The ECM of the renal cortex and fibronectin expression of MMCs were analyzed through immunohistochemistry and western blotting. Arginase 1 and inducible NO synthase expressions of MDSCs were evaluated using quantitative reverse-transcriptase PCR. Cytokines released from MMCs were examined using a cytokine array assay.ResultsMDSCs in the diabetic mice were redistributed from the bone marrow into peripheral organs. An increase in fibronectin production was also observed in the renal glomerulus. MMCs in vitro produced more fibronectin and proinflammatory cytokines, such as macrophage inflammatory protein-2, RANTES, and stromal-cell-derived factor-1, under hyperglycemic conditions. The adoptive transfer of cytokine-induced MDSCs into STZ-induced mice normalized the glomerular filtration rate to reduce the kidney to body weight ratio and decrease fibronectin production in the renal glomerulus, ameliorating renal fibrosis. These results demonstrate the anti-inflammatory properties of cytokine-induced MDSCs and offer an alternative immunotherapy protocol for the management of diabetic nephropathy.ConclusionsThe application of cytokine-induced MDSCs provides a promising treatment for renal fibrosis and the prevention of diabetic nephropathy.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0915-0) contains supplementary material, which is available to authorized users.

The tumor microenvironment, which consists of fibroblasts, smooth muscle cells, endothelial cells, immune cells, epithelial cells, and extracellular matrices, plays a crucial role in tumor progression. Hepatic stellate cells (HSCs), a class of unique liver stromal cells, participate in immunomodulatory activities by inducing the apoptosis of effector T-cells, generation of regulatory T-cells, and development of myeloid-derived suppressor cells (MDSCs) to achieve long-term survival of islet allografts. This study provides in vitro and in vivo evidences that HSCs induce the generation of MDSCs to promote hepatocellular carcinoma (HCC) progression through interleukin (IL)-6 secretion. HSC-induced MDSCs highly expressed inducible nitric oxide synthase (iNOS) and arginase 1 mRNA and presented potent inhibitory T-cell immune responses in the tumor environment. Wild-type HSC-induced MDSCs expressed lower levels of CD40, CD86, and MHC II, and a higher level of B7-H1 surface molecules, as well as increased the production of iNOS and arginase I compared with MDSCs induced by IL-6-deficient HSCs in vitro. A murine-transplanted model of the liver tumor showed that HCCs cotransplanted with HSCs could significantly enhance the tumor area and detect more MDSCs compared with HCCs alone or HCCs cotransplanted with HSCs lacking IL-6. In conclusion, the results indicated that MDSCs are induced mainly by HSCs through IL-6 signaling and produce inhibitory enzymes to reduce T-cell immunity and then promote HCC progression within the tumor microenvironment. Therapies targeting the pathway involved in MDSC production or its immune-modulating pathways can serve as an alternative immunotherapy for HCC.

Background: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients.Methods: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared.Results: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC.Conclusions: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients.

No abstract

Background: Hyperglycemia at the time of hospital admission is associated with higher morbidity and mortality rates in patients with traumatic brain injury (TBI). Using data from the Chang Gung Research Database (CGRD), this study aimed to compare mortality outcomes between patients with stress-induced hyperglycemia (SIH), diabetic hyperglycemia (DH), and nondiabetic normoglycemia (NDN). The study occurred at Keelung, Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals (CGMHs). Methods: A total of 1166, 6318, 3622, and 5599 health records from Keelung, Linkou, Chiayi, and Kaohsiung CGMHs, respectively, were retrieved from the CGRD for hospitalized patients with TBI between January 2001 and December 2015. After propensity score matching for sex, age, and Glasgow Coma Scale (GCS) score, the matched cohorts were compared to evaluate differences in the primary outcome between patients with SIH, DH, and NDN. In-hospital mortality was the primary outcome. Results: The analysis of matched patient populations revealed that at the Kaohsiung CGMH, patients with SIH had 1.63-fold (95% CI: 1.09–2.44; p = 0.017) and 1.91-fold (95% CI: 1.12–3.23; p = 0.017) higher odds of mortality than patients with NDN and DH, respectively. Similar patterns were found at the Linkou CGMH; patients with SIH had higher odds of mortality than patients with NDN and DH. In contrast, at the Keelung CGMH, patients with SIH had significantly higher odds of mortality than those with NDN (OR: 3.25; 95% CI: 1.06–9.97; p = 0.039). At the Chiayi CGMH, there were no significant differences in mortality rates among all groups. Conclusions: This study’s results suggest that SIH and DH differ in their effect on the outcomes of patients with TBI. The results were similar between medical centers but not nonmedical centers; in the medical centers, patients with SIH had significantly higher odds of mortality than patients with either NDN or DH.

No abstract

No abstract