Search

Asthma is the most common chronic respiratory disease in children, which is mainly pathophysiologically charactrized by reversible airflow limitation. Bronchodilation test is one of the methods to evaluate the reversible degree of airflow limitation, which plays an important role in the diagnosis and treatment of asthma. However, different pulmonary function testing methods should be employed for children of different ages due to their specific characteristics. The corresponding cut-off value for positive bronchodilation test for children is different from that for adults. Bronchodilation test can also evaluate the control situation, and predict therapeutic responses and future risks. In this article, bronchodilation test of different pulmonary function testing methods and its application in the assessment and management of pediatric asthma were reviewed.

Infantile malignant osteopetrosis （IMO） is mainly manifested with the increased bone density, smaller bone marrow cavity and severe extramedullary hematopoiesis. At present, hematopoietic cell transplantation represents the only curative treatment for IMO. In this article, we reported a 3-month-old male infant with IMO. He was admitted due to abnormal hemograms for 10 d at 9 d after incarcerated right oblique inguinal hernia surgery. Clinical manifestations mainly included inspiratory dyspnea, hepatosplenomegaly and decreased levels of hemoglobin and platelets. Thoracic and pelvic X-ray examination and CT scan of head and neck revealed increased bone density. High-resolution clinical exome sequencing detected homozygous mutation of c. 1480delC （p.Q494Sfs*34） in the T-cell immune regulator 1（TCIRG1） gene, which has not been reported yet. Sequencing data showed that this mutation was inherited from his parents （heterozygous status in his parents, his parents were cousins）.

Depleted uranium (DU) retains the radiological toxicities, which accumulates preferentially in the kidneys. Hedgehog (Hh) pathway plays a critical role in tissue injury. However, the role of Hh in DU‐induced nephrotoxicity was still unclear. This study was carried out to investigate the effect of Gli2, which was an important transcription effector of Hh signaling, on DU induced nephrotoxicity. To clarify it, CK19 positive tubular epithelial cells specific Gli2 conditional knockout (KO) mice model was exposed to DU, and then histopathological damage and Hh signaling pathway activation was analyzed. Moreover, HEK‐293 T cells were exposed to DU with Gant61 or Gli2 overexpression, and cytotoxicity of DU as analyzed. Results showed that DU caused nephrotoxicity accompanied by activation of Hh signaling pathway. Meanwhile, genetic KO of Gli2 reduced DU‐induced nephrotoxicity by normalizing biochemical indicators and reducing Hh pathway activation. Pharmacologic inhibition of Gli1/2 by Gant61 reduced DU induced cytotoxicity by inhibiting apoptosis, ROS formation and Hh pathway activation. However, overexpression of Gli2 aggravated DU‐induced cytotoxicity by increasing the levels of apoptosis and ROS formation. Taken together, these results revealed that Hh signaling negatively regulated DU‐inducted nephrotoxicity, and that inhibition of Gli2 might serve as a promising nephroprotective target for DU‐induced kidney injury. [ABSTRACT FROM AUTHOR]

Three curcumin analogs(S1-S3) containing sulfone were investigated for their effects on human prostate cancer PC-3, colon cancer HT-29, lung cancer H1299 and pancreatic cancer BxPC-3 cells. The three compounds were approximately 16-to 96-fold more active than curcumin in these cell lines as determined by the MTT assay. The effects of these compounds on cell growth were further studied in prostate cancer PC-3 cells in both two dimensional (2D) and three dimensional (3D) cultures. S1-S3strongly inhibited the growth and induced cell death in PC-3 cells, and the effects of these compounds were associated with suppression of nuclear factor kappa B (NF-κB) transcriptional activity. Moreover, treatment of PC-3 cells with all three compounds caused a decrease in the level of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) (Tyr705),but not p-STAT3(Ser727). Only S1and S2decreased the presence of phosphorylated Akt (p-Akt) in PC-3 cells. These curcumin analogs warrant further in vivo studies for anticancer activities in suitable animal models.

The mechanisms by which the ATG16L1T300A polymorphism affects cell function and causes an increased risk for the development of Crohn disease remain incompletely understood. Here we report that healthy individuals and mice bearing this polymorphism, even as heterozygotes, manifest enhanced TLR, and NLR cytokine and chemokine responses due to increased activation of NFKB. We elucidated the mechanism of the NFKB abnormality and found that in the ATG16L1T300A cell, there is enhanced polyubiquitination of TRAF6 or RIPK2 resulting from the accumulation of SQSTM1/p62. Indeed, knockout of Sqstm1 in autophagy-deficient cells almost completely normalized TRAF6 or RIPK2 polyubiquitination and NFKB activation in these cells. Thus, by identifying that autophagy is a pathway-intrinsic homeostatic mechanism that restricts excessive TLR- or NLR-mediated inflammatory signaling, our findings shed new light on how the ATG16L1T300A polymorphism sets the stage for the occurrence of Crohn disease. Abbreviations: 3-MA: 3-methyladenine; ATG16L1: autophagy related 16 like 1; ATG7: autophagy related 7; BMDM: bone marrow-derived macrophage; CD: Crohn disease; CXCL: C-X-C motif chemokine ligand; IBD: inflammatory bowel disease; iBMDM: immortalized mouse BMDM; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; KI: knockin; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LPS: lipopolysaccharide; MDP: muramyl dipeptide; MEF: mouse embryonic fibroblast; NFKB/NF-κB: nuclear factor kappa B; NFKBIA/IKBA: NFKB inhibitor alpha; NLR: NOD-like receptor; NOD: nucleotide-binding oligomerization domain containing; RIPK2: receptor interacting serine/threonine kinase 2; SNP: single nucleotide polymorphism; SQSTM1/p62: sequestosome 1; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor; TRAF6: TNF receptor associated factor 6; Ub: ubiquitin; WT: wild type [ABSTRACT FROM AUTHOR]

Two new pyrone derivatives, 2-(12S-hydroxypropyl)-3-hydroxy-methyl-6-hydroxy-7-methoxychromone (1), and (±)-pyrenocine S (5), together with five known compounds xanthoradone A (2), (+)-3,3′,7,7′,8,8′-hexahydroxy-5,5′-dimethyl-bianthra-quinone (3), butyrolactone-I (4), pyrenocine A (6), and (±)-pyrenocine E (7) were obtained from the mangrove endophytic fungus Aspergillus sydowii #2B. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis and comparison data with of literatures. Compounds 2, 3, 4, 5, 6 and 7 showed cytotoxicities against prostate cancer VCaP cells with IC50 values of 4.19 ± 1.02, 33.36 ± 1.42, 1.92 ± 0.82, 20.06 ± 2.01, 7.92 ± 0.86, and 10.13 ± 0.88 μM respectively, while compound 1 showed no cytotoxic activity. Compounds 1, 3, 6, and 7 exhibited weak inhibition effects against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 246.7 cells with IC50 values of 40.15, 28.69, 25.25 and 43.08 μM respectively. [ABSTRACT FROM AUTHOR]

Exposure to carbon blacks (CBs) has been associated with the progression of pulmonary fibrosis, whereas the mechanism is still not clear. We therefore aimed to investigate the effect of RhoA/ROCK pathway on pulmonary fibrosis caused by CBs exposure. Western blot analysis indicated that CBs could promote the activation of RhoA/ROCK pathway and phosphorylation of p65 and IκBα in mice lung. However, ROCK inhibitor Y‐27632 could attenuate phosphorylation levels of p65 and IκBα and restore histopathological changes of the lung tissue. Then, we evaluated the effect of RhoA/ROCK pathway on pulmonary fibrosis by detecting the expression levels of α‐SMA, vimentin, and Collagen type‐I (Col‐I), which could be partly inhibited by Y‐27632. It was assumed that inhibition of ROCK could be a promising therapeutic candidate for CBs‐induced pulmonary fibrosis, which possibly through the blockage of RhoA/ROCK/NF‐κB pathway. [ABSTRACT FROM AUTHOR]