Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis. AIM: To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC. METHODS: The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed. RESULTS: In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II vs stage III vs stage IV, P < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different (P < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different (P < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant (P < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant (P < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%). CONCLUSION: In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.

Clinical characteristics and biomarkers analysis of asthma inflammatory phenotypes.

Aim: Asthma inflammatory phenotypes facilitate treatment, their clinical characteristics and biomarkers were analyzed. Materials & methods: A total of 176 asthmatics were divided into eosinophilic asthma (EA), neutrophilic asthma (NA), paucigranulocytic asthma and mixed-granulocytic asthma by induced sputum. Results: EA, NA and paucigranulocytic asthma patients were 65 (36.9%), 31 (17.6%) and 75 (42.6%). Sputum IL-5 and IL-13, blood IL-13, fractional exhaled nitric oxide (FeNO) were related to EA, the areas under the receiver operating characteristic curve were 0.790, 0.846, 0.828, 0.830, combined FeNO with blood IL-13 was 0.872. Sputum and blood IL-8, blood IL-17 were related to NA, their area under the receiver operating characteristic curve was 0.939, 0.844, 0.821, combined blood IL-8 with IL-17 was 0.882. Conclusion: Blood IL-13 and FeNO, blood IL-8 and IL-17 were alternative biomarkers of EA and NA, respectively.

4-Benzyl-1-p-tolyl-1H-1,2,4-triazol-5(4H)-one.

In the title compound, C(16)H(15)N(3)O, the triazole ring makes dihedral angles of 7.08 (2) and 74.53 (3)° with the two outer aromatic rings. The crystal packing is stabilized by very short inter-molecular C-H⋯O hydrogen bonds and weak π-π stacking inter-actions [centroid-to-centroid distance 3.632 (3) Å], resulting in the formation of zigzag chains parallel to the b axis.

Peripheral whole blood lncRNA expression analysis in patients with eosinophilic asthma.

Long noncoding RNA (lncRNA) plays roles in many diseases including asthma. Several lncRNAs function in the early differentiation of T-helper cells. lncRNA controls gene transcription, protein expression, and epigenetic regulation. Of the 4 asthma phenotypes, eosinophilic asthma (EA) is the most common. However, the lncRNAs associated with eosinophilic asthma have yet to be identified.We designed a study to identify the circulating lncRNA signature in EA samples. We tested whether significant differences in lncRNA expression were observed between blood samples from patients with EA and healthy individuals (control). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the lncRNA-mRNA (messenger RNA) co-expression network. lncRNA expression was measured using quantitative real-time PCR (polymerase chain reaction).A total of 41 dysregulated lncRNAs and 762 dysregulated mRNAs (difference ≥ 2-fold) were found in EA compared to control samples. GO terms and KEGG pathway annotation data revealed that several lncRNAs are significantly associated with EA. KEGG pathway annotation indicated that the pathways most enriched in EA were measles, T cell receptor signaling pathway, peroxisome proliferator activated-receptors (PPAR) signaling pathway, Fc gamma R-mediated phagocytosis, NF (nuclear factor) kappa B signaling pathway, chemokine signaling pathway, and primary immunodeficiency. Using qRT-PCR, lncRNA was confirmed to differ significantly between EA and control samples.The results presented here show that several lncRNAs may take part in the immune regulation of EA. Whether these lncRNAs can be used as biomarkers needs further study.

Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine: a widely used inhibitor of autophagy.

The true programmed mechanisms of delayed neuronal death induced by global cerebral ischemia/reperfusion injury remain incompletely characterized. Autophagic cell death and programmed necrosis are 2 kinds of programmed cell death distinct from apoptosis. Here, we studied the death mechanisms of hippocampal cornu ammonis 1 neuronal death after a 20-minute severe global ischemia/reperfusion injury in young adult rats and the effects of 3-methyladenine (3-MA), a widely used inhibitor of autophagy. The morphological changes detected by electron microscopy, together with the activation of autophagy, transferase-mediated UTP nick end-labeling-positive neurons, and delayed death, demonstrated that cornu ammonis 1 neuronal death induced in this paradigm was programmed necrosis. No significant activation of caspase-3 after injury was detected by Western blot and immunohistochemistry. Treatment with 3-MA provided time-dependent protection against cornu ammonis 1 neuronal death at 7 days of reperfusion when it was administered before ischemia; administration 60 minutes after reperfusion was not beneficial. The redistribution of the lysosomal enzyme cathepsin B after injury was inhibited by 3-MA administered before ischemia, suggesting that this might be another important mechanism for the protective effect of 3-MA in ischemic neuronal injury.

Bicyclol attenuates oxidative stress and neuronal damage following transient forebrain ischemia in mouse cortex and hippocampus.

To assess its potential neuroprotective effect against ischemia/reperfusion (IR) injury in mice, bicyclol was administered intragastrically once a day for 3 days. After 6h of bicyclol pretreatment on the third day, forebrain ischemia was induced for 1h by bilateral occlusion of the carotid arteries. After different times of reperfusion, the histopathological changes and the levels of mitochondria-generated reactive oxygen species (ROS), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the cortex and hippocampus were measured. We found that extensive neuronal death occurred in the cortex and the CA1 area of the hippocampus at day 7 after IR and that bicyclol significantly attenuated IR-induced neuronal death in a dose-dependent manner. We also found that pretreatment with bicyclol dose dependently decreased the generation of ROS and the MDA content and reduced the compensatory increase in SOD activity in the cortex and hippocampus at 4h of reperfusion. These results suggest that bicyclol protects the mouse brain against cerebral IR injury by attenuating oxidative stress and lipid peroxidation.