Body composition parameters correlate with the endoscopic severity in Crohn’s disease patients treated with infliximab

BackgroundThe disease activity status and behavior of Crohn’s disease (CD) can reflect the severity of the disease, and changes in body composition are common in CD patients.AimsThe aim of this study was to investigate the relationship between body composition parameters and disease severity in CD patients treated with infliximab (IFX).MethodsPatients with CD assessed with the simple endoscopic score (SES-CD) and were treated with IFX were retrospectively collected, and body composition parameters at the level of the 3rd lumbar vertebrae were calculated from computed tomography (CT) scans of the patients. The correlation of patients’ body composition parameters with disease activity status and disease behavior was analyzed, and the diagnostic value of the relevant parameters was assessed using receiver operating characteristic (ROC) curves.ResultsA total of 106 patients were included in this study. There were significant differences in the subcutaneous adiposity index (SAI) (p = 0.010), the visceral adiposity index (VAI) (p < 0.001), the skeletal muscle mass index (SMI) (p < 0.001), and decreased skeletal muscle mass (p < 0.001) among patients with different activity status. After Spearman and multivariate regression analysis, SAI (p = 0.006 and p = 0.001), VAI (p < 0.001 and p < 0.001), and SMI (p < 0.001and p = 0.007) were identified as independent correlates of disease activity status (both disease activity and moderate-to-severe activity), with disease activity status independently positively correlated with SAI and SMI and independently negatively correlated with VAI. In determining the disease activity and moderate-to-severe activity status, SMI performed best relative to SAI and VAI, with areas under the ROC curve of 0.865 and 0.801, respectively. SAI (p = 0.015), SMI (p = 0.011) and decreased skeletal muscle mass (p = 0.027) were significantly different between different disease behavior groups (inflammatory disease behavior group, complex disease behavior group) but were not independent correlates (p > 0.05).ConclusionBody composition parameters of CD patients treated with IFX correlate with the endoscopic disease severity, and SMI can be used as a reliable indicator of disease activity status

Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study

<p>Abstract</p> <p>Background</p> <p>Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-<it>α </it>gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis.</p> <p>Methods</p> <p>The association between genetic polymorphisms of <it>TNF-α </it>gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of <it>TNF-α </it>gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data.</p> <p>Results</p> <p>Compared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%<it>CI</it>) of 0.95(0.90–0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%<it>CI</it>) of 5.33(1.39–20.45) and 5.67(2.74–11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18–23.46) and the combined (CT and CC) genotype OR was 6.0 (95%<it>CI </it>1.60–22.55) at -1031 site of <it>TNF-α </it>gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%<it>CI</it>) of 6.42(1.53–26.88) and the adjusted OR was 8.40(95%CI 1.76–40.02) in cured SARS patients compared to CC genotype.</p> <p>Conclusion</p> <p>SNPs of <it>TNF-α </it>gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients.</p

Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate

Abstract The ammonium glycyrrhizinate-loaded chitosan nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size and zeta potential of nanoparticles were determined, respectively, by dynamic light scattering (DLS) and a zeta potential analyzer. The effects, including chitosan molecular weight, chitosan concentration, ammonium glycyrrhizinate concentration and polyethylene glycol (PEG) on the physicochemical properties of the nanoparticles were studied. These nanoparticles have ammonium glycyrrhizinate loading efficiency. The encapsulation efficiency decreased with the increase of ammonium glycyrrhizinate concentration and chitosan concentration. The introduction of PEG can decrease significantly the positive charge of particle surface. These studies showed that chitosan can complex TPP to form stable cationic nanoparticles for subsequent ammonium glycyrrhizinate loading

Fluoropolymer Coated DNA Nanoclews for Volumetric Visualization of Oligonucleotides Delivery and Near Infrared Light Activated Anti‐Angiogenic Oncotherapy

Abstract The potential of microRNA regulation in oncotherapy is limited by the lack of delivery vehicles. Herein, it is shown that fluoropolymer coated DNA nanoclews (FNCs) provide outstanding ability to deliver oligonucleotide through circulation and realize near infrared (NIR) light activated angiogenesis suppression to abrogate tumors. Oligonucleotides are loaded in DNA nanoclews through sequence specific bindings and then a fluorinated zwitterionic polymer is coated onto the surface of nanoclews. Further incorporating quantum dots in the polymer coating endows the vectors with NIR‐IIb (1500–1700 nm) fluorescence and NIR light triggered release ability. The FNC vector can deliver oligonucleotides to cancer cells systemically and realize on‐demand cytosolic release of the cargo with high transfection efficiency. Taking advantage of the NIR‐IIb emission, the whole delivery process of FNCs is visualized volumetrically in vivo with a NIR light sheet microscope. Loaded by FNCs, an oligonucleotide can effectively silence the target miRNA when activated with NIR light, and inhibit angiogenesis inside tumor, leading to complete ablation of cancer. These findings suggest FNCs can be used as an efficient oligonucleotide delivery platform to modulate the expression of endogenous microRNA in gene therapy of cancer

Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors

AbstractTo explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory activity on CDK9 and obvious anti-proliferative activity in cell culture. Moreover, two new compounds suppressed cell proliferation of multiple human pancreatic cancer cell lines. The most potent compound 2g inhibited cancer cell proliferation by blocking Rb phosphorylation and induced apoptosis via downregulation of CDK9 downstream proteins Mcl-1 and c-Myc in MIA PaCa-2 cells. CDK9 knockdown experiment suggests its anti-proliferative activity is mainly mediated by CDK9. Additionally, 2g displayed moderate tumour inhibition effect in AsPC-1 derived xenograft mice model. Altogether, this study provided a new start for further optimisation to develop potential CDK inhibitor candidates for PDAC treatment by alone or combination use