Acute-On-Chronic Liver Failure ; diagnosis ; Humans

MicroRNAs (miRNAs) are small non-coding RNAs that are important in regulating metabolic stress. In this study, we determined the expression and structural characteristics of 20 miRNAs in brown (BAT) and white adipose tissue (WAT) during torpor in thirteen-lined ground squirrels. Using a modified stem-loop technique, we found that during torpor, expression of six miRNAs including let-7a, let-7b, miR-107, miR-150, miR-222 and miR-31 was significantly downregulated in WAT (P < 0.05), which was 16%–54% of euthermic non-torpid control squirrels, whereas expression of three miRNAs including miR-143, miR-200a and miR-519d was found to be upregulated by 1.32–2.34-fold. Similarly, expression of more miRNAs was downregulated in BAT during torpor. We detected reduced expression of 6 miRNAs including miR-103a, miR- 107, miR-125b, miR-21, miR-221 and miR-31 (48%–70% of control), while only expression of miR-138 was significantly upregulated (2.91 ± 0.8-fold of the control, P <0.05). Interestingly, miRNAs found to be downregulated in WAT during torpor were similar to those dysregulated in obese humans for increased adipogenesis, whereas miRNAs with altered expression in BAT during torpor were linked to mitochondrial b-oxidation. miRPath target prediction analysis showed that miRNAs downregulated in both WAT and BAT were associated with the regulation of mitogen- activated protein kinase (MAPK) signaling, while the miRNAs upregulated in WAT were linked to transforming growth factor b (TGFb) signaling. Compared to mouse sequences, no unique nucleotide substitutions within the stem-loop region were discovered for the associated pre-miRNAs for the miRNAs used in this study, suggesting no structure-influenced changes in pre-miRNA processing efficiency in the squirrel. As well, the expression of miRNA processing enzyme Dicer remained unchanged in both tissues during torpor. Overall, our findings suggest that changes of miRNA expression in adipose tissues may be linked to distinct biological roles in WAT and BAT during hibernation and may involve the regulation of signaling cascades.

With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech-niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons (MBs), a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.

INTRODUCTIONThis study retrospectively evaluated CT-guided thoracic biopsies for diagnostic yield, accuracy and complications.

MATERIALS AND METHODSA retrospective analysis of 384 patients (mean age 62.7 years; male/female = 251/133) who underwent 399 CT-guided thoracic biopsies were performed for evaluating diagnostic yield, accuracy and complications. Correlations between patients age, procedure factors (biopsy-needle size, number of passes, lesion-size, lesion-depth and traversed lung-length) and complications such as pneumothorax, haemothorax and haemoptysis were evaluated. A comparison between fine needle aspiration (FNA) group and core ± FNA group for diagnostic yield and complications was also performed.

RESULTSFNA was performed in 349 patients and core ± FNA in 50 patients. The biopsy samples were adequate in 91.9% and the diagnostic accuracy for malignant lesions was 96.8% with 95.7% sensitivity and 100% specificity. Pneumothorax (detected on CT) occurred in 139 cases (34.8%) and only 12 (3.0%) required insertion of an intercostals drain. Mild haemoptysis occurred in 13 patients (3.2%) and small haemothoraces in 2 patients. Pneumothorax occurrence was significantly associated with the traversed lung-length (>3mm), lesion-size (≤33 mm) and lesion-depth (≥60mm) (P <0.05). Haemoptysis occurrence was also significantly associated with traversed lunglength (>3mm) and lesion-size (≤33 mm) (P <0.05). There was no significant difference between diagnostic yield and complication rate between FNA and core ± FNA groups.

CONCLUSIONCT-guided thoracic biopsy is a safe procedure with high diagnostic yield and low risk of significant complications. Traversed lung-length and smaller lesion size are associated with occurrence of pneumothorax and haemoptysis.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Image-Guided Biopsy ; adverse effects ; methods ; Lung Neoplasms ; diagnosis ; Male ; Middle Aged ; Postoperative Complications ; Reproducibility of Results ; Retrospective Studies ; Tomography, X-Ray Computed

BACKGROUND: Anti-IgE mAb which binds circulating but not receptor-bound IgE has been shown to be effective in treatment for asthma and other allergic diseases. However, the mechanisms by which anti-IgE mAb influences the pathophysiological responses are remained to be illustrated. This study was undertaken to examine the therapeutic efficacy of non-anaphylactogenic anti-mouse IgE mAb using murine models of IgE-induced systemic fatal anaphylaxis. METHODS: Active systemic anaphylaxis was induced by either penicillin V (Pen V) or OVA and passive systemic anaphylaxis was induced by either anaphylactogenic anti-mouse IgE or a mixture of anti-chicken gamma globulin (CGG) IgG1 mAb and CGG. The binding of the Fc portion of anti-IgE to CHO-stable cell line expressing mouse FcgammaRIIb was examined using flow cytometry. Fc fragments of anti-IgE mAb were prepared using papain digestion. The expression of phosphatases in lungs were assessed by Western blotting and immunohistochemistry. RESULTS: Anti-IgE mAb prevented IgE- and IgG-induced active and passive systemic fatal reactions. In both types of anaphylaxis, anti-IgE mAb suppressed antigen-specific IgE responses, but not those of IgG. Anti-IgE mAb neither prevented anaphylaxis nor suppressed the IgE response in FcgammaRIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine FcgammaRIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of FcgammaRIIb-associated phosphatases such as src homology 2 domain-containing inositol 5-phosphatase (SHIP) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). CONCLUSION: Anti-IgE mAb prevented anaphylaxis by delivering nonspecific inhibitory signals through the inhibitory IgG receptor, FcgammaRIIb, rather than targeting IgE.
Anaphylaxis* ; Animals ; Asthma ; Blotting, Western ; Cell Line ; CHO Cells ; Cricetinae ; Digestion ; Down-Regulation ; Flow Cytometry ; gamma-Globulins ; Immunoglobulin E ; Immunoglobulin Fc Fragments ; Immunoglobulin G* ; Immunohistochemistry ; Inositol ; Lung ; Mice* ; Ovum ; Papain ; Penicillin V ; Phosphoric Monoester Hydrolases

Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Vesico-Ureteral Reflux ; diagnosis ; therapy

OBJECTIVETo measure the bone-prosthetic implant interface micromovement during the application of physiological load by using a material testing system (MTS).

METHODSThe cadaveric hip specimens were used to simulate a single leg stance and the joint in the neutral position. Micromovement was recorded via a 3-dimensional transducer in the acetabula of postmortem specimens, which had been preserved in formalin. The study data of the cemented and uncemented prosthsis refereed to the lone-term clinical process and the radiological status and experimental results.

RESULTSCemented cups showed higher transverse relative motion up to 90 microm, whereas the maximum transverse movement of the non-cemented cup was 60 microm. Orthogonal motion perpendicular to the implant surface showed compression for all cups at all sites.

CONCLUSIONThe results indicate that there are large differences in survival time between 2 groups. That could not be compared statistically in secondary stability. Nevertheless, according to the results, the amount of micromotion of press-fit cup is relatively less than that of cemented polyethylene cup, which is instrumental in bone ingrowth and secondary stability.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; methods ; Biomechanical Phenomena ; Bioprosthesis ; Bone Cements ; Female ; Hip Prosthesis ; Humans ; Prosthesis Failure ; Weight-Bearing

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
Animals ; Anxiety/etiology* ; Chronic Pain/etiology* ; GABAergic Neurons ; Gyrus Cinguli/metabolism* ; Hyperalgesia/metabolism* ; Pancreatitis, Chronic/pathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Trinitrobenzenesulfonic Acid/toxicity*

Studies have recently suggested that the coupling mechanism of bone formation and bone resorption are affected by particulate wear debris inducing aseptic loosening around the bone-prosthesis microenviroment. There may be direct impacts on osteoblasts, resulting in net decrease in bone formation. In addition, the influences of particulate wear debris in different size on the osteogenesis should be various. In order to investigate the hypothesis that particulate wear debris derived from prosthetic biomaterials affects the osteogenesis of osteblasts, we studied the influence of different-sized titanium particles loading on the osteoblastic differentiation by assaying the secretion of alkaline phosphatase (ALP), osteocalcin (OCN), N-terminal type I procollagen (PINP), and on the osteoblastic mineralization with the use of calcified node number, calcified node area and Alizarin Red S (ARS) concentration. Upon in vitro culture in the absence of titanium particles, we observed that cultures of osteoblasts isolated from newborn Japanese rabbits' cranium were excellently capable of differentiation and mineralization. Phi6.9 microm titanium particles did not evidently alter osteoblastic differentiation and mineralization. In comparison, phi2.7 microm and phi0.9 microm titanium particles, especially phi0.9 microm (submicron), significantly suppressed ALP expression, reduced PINP production, decreased OCN secretion and inhibited matrix mineralization. Results of transmission electron microscopy (TEM) of titanium particles-loaded osteoblastic cultures revealed that osteoblasts phagocytized titanium particles and exhibited ultrastructional changes consistent with cellular dysfuction. Combined with our previous studies in vitro findings, these results suggest that particles size play a key role in the process of aseptic loosening, which submicron particles are closely associated with inhibition of bone formation while bigger particles with enhancement of bone resorption. Further understanding the nature of osteoblastic bioreactivity to different-size wear particles should provide additional insights into mechanisms underlying aseptic loosening.
Animals ; Animals, Newborn ; Calcification, Physiologic ; drug effects ; Cell Differentiation ; Cells, Cultured ; Female ; Male ; Osteoblasts ; cytology ; Osteocalcin ; biosynthesis ; Osteogenesis ; drug effects ; Particle Size ; Prostheses and Implants ; Prosthesis Failure ; Rabbits ; Titanium ; pharmacology

Ghrelin is a 28-amino-acid peptide that plays multiple roles in humans and other mammals. The functions of ghrelin include food intake regulation, gastrointestinal (GI) motility, and acid secretion by the GI tract. Many GI disorders involving infection, inflammation, and malignancy are also correlated with altered ghrelin production and secretion. Although suppressed ghrelin responses have already been observed in various GI disorders, such as chronic gastritis, Helicobacter pylori infection, irritable bowel syndrome, functional dyspepsia, and cachexia, elevated ghrelin responses have also been reported in celiac disease and inflammatory bowel disease. Moreover, we recently reported that decreased fasting and postprandial ghrelin levels were observed in female patients with functional dyspepsia compared with healthy subjects. These alterations of ghrelin responses were significantly correlated with meal-related symptoms (bloating and early satiation) in female functional dyspepsia patients. We therefore support the notion that abnormal ghrelin responses may play important roles in various GI disorders. Furthermore, human clinical trials and animal studies involving the administration of ghrelin or its receptor agonists have shown promising improvements in gastroparesis, anorexia, and cancer. This review summarizes the impact of ghrelin, its family of peptides, and its receptors on GI diseases and proposes ghrelin modulation as a potential therapy.
Animals ; Anorexia ; Appetite Regulation ; Cachexia ; Celiac Disease ; Dyspepsia ; Fasting ; Female ; Gastritis ; Gastrointestinal Diseases ; Gastrointestinal Tract ; Gastroparesis ; Ghrelin ; Helicobacter pylori ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Irritable Bowel Syndrome ; Mammals ; Peptides ; Receptors, Ghrelin