Saffron Petal, an Edible Byproduct of Saffron, Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting Macrophage Activation and Regulating Gut Microbiota.

Saffron petal (SP) is an agricultural byproduct in the process of the crude drug saffron, accounting for 90% of the dry weight of saffron flowers. To promote the utilization of SP in the food and pharmaceutical industries, its anti-inflammatory activities were evaluated on LPS-activated RAW 264.7 cells and DSS-challenged colitic mice. The results indicated that the SP extract had a notable effect in alleviating the clinical manifestations of colitis, such as reduction in body weight, improvement in disease activity index, mitigation of colon shortening, and alleviation of colon tissue damage. Moreover, SP extract significantly suppressed macrophage infiltration and activation, evidenced by a decrease in colonic F4/80 macrophages and suppression of the transcription and secretion of colonic tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in DSS-challenged colitic mice. In vitro, SP extract also significantly suppressed nitric oxide production, COX-2 and iNOS expressions, and TNF-α and IL-1ß transcription of activated RAW 264.7 cells. Network pharmacology-guided research identified that SP extract significantly downregulated Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro. In parallel, SP extract also effectively corrected microbial dysbiosis by increasing the abundance of Bacteroides acidifaciens, Bacteroides vulgatus, Lactobacillus murinus, and Lactobacillus gasseri. These findings indicate that the effectiveness of SP extract in treating colitis is demonstrated by its ability to reduce macrophage activation, inhibit the PI3K/Akt and MAPK pathways, and regulate gut microbiota, suggesting that SP extract holds great potential as a therapeutic option for colitis.

[Analysis of clinical features and genetic variants in a child with autosomal recessive cutis laxa due to variants of ATP6V0A2 gene].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child featuring autosomal recessive cutis laxa (ARCL). METHODS: Clinical data of the patient was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband, his sister and parents. Candidate variant was verified by Sanger sequencing. RESULTS: The 5 years and 2 month old child, was 109.5 cm tall (40% centile) and 14.2 kg in weight (< 3% centile). Physical examination discovered facial dysmorphisms including downslanting palpebral fissure, hypertelorism, broad nasal bridge, prominent forehead, long philtrum, obvious loose and wrinkled of abdominal and groin skin. He also had previous history of cryptorchidism and umbilical hernia. Trio-WES revealed that the child harbored compound heterozygous variants c.1421_1424delAGTC (p.Val476Thrfs*71) and c.2293+1G>A of the ATP6V0A2 gene, both of which were unreported previously. In addition to our patient, 75 cases of ATP6V0A2 gene-related ARCL have so far been diagnosed, with main features including cutis laxa [100% (75/75)], facial dysmorphism [78.7% (59/75)] and delayed closure/large anterior fontanelle [65.3% (49/75)]. Typical facial features have included downslanting palpebral fissures [57.3% (43/75)], broad nasal bridge [40.0% (30/75)] and long face [34.7% (26/75)]. CONCLUSION: Patients presenting with generalized skin wrinkling, facial dysmorphism, delayed closure/large anterior fontanelle, mental retardation, global developmental disabilities and seizures should be considered for ATP6V0A2 gene-related ARCL. Exome sequencing may facilitate the identification of genetic etiology, to confirm the diagnosis.

Routine blood parameters are helpful for early identification of influenza infection in children.

BACKGROUND: Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), lymphocytes multiplied by platelets (LYM*PLT) and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children. METHODS: We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 h of the onset of fever for influenza virus infection. RESULTS: The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the > 6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the > 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924. CONCLUSIONS: Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly in children older than 6 years with influenza A virus infection.

[Genetic variant analysis of a neonate with Cornelia de Lange syndrome].

OBJECTIVE: To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS). METHODS: Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing. RESULTS: The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected. CONCLUSION: The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.

Heparin improves alveolarization and vascular development in hyperoxia-induced bronchopulmonary dysplasia by inhibiting neutrophil extracellular traps.

The objective of this study was to assess the role of NETs in BPD of hyperoxia-induced rat model and the effect of heparin on alveolarization and vascular development in BPD. The neonatal rats exposed to 90% oxygen continuously for 7 days to mimic BPD, meanwhile, the rats were injected by different doses of histones to evaluate the impact on lung injury. The newborn rats exposed to hyperoxia were injected by different doses of heparin (250 U/kg, 500 U/kg) or anti-H4 antibody to evaluate the effect of heparin. Histones and hyperoxia impaired alveolarization with the increase of mean linear intercept (MLI) and the decrease of radial alveolar count (RAC), decreased lung angiogenesis with the decrease expression of VEGF, and increased the expression of NETs, histones and pro-inflammatory factor. However, low dose heparin (250U/kg) administration enhanced survival, improved alveolarization and vascular development in hyperoxia-induced BPD, as well as reduced expression of NETs, histones and pro-inflammatory factor. We concluded that heparin improves alveolarization and vascularization in BPD by inhibiting NETs.

Human ß-Defensin-2 Improves Hyperoxia-Induced Lung Structural and Functional Injury in Neonatal Rats.

BACKGROUND Bronchopulmonary dysplasia (BPD) is a major complication of extreme prematurity, characterized by alveolar simplification and pulmonary malfunction. Hyperoxia-induced lung injury in neonatal rats has been used as a model of BPD, as indicated by lung architectural change and alveolar simplification that resembles clinical feature of BPD. ß-defensin-2 (BD2) plays an important role in lung diseases by inhibiting inflammation response. However, little is known about its role in BPD. The aim of this study was to determine the effect of human BD2 (hBD2) gene on hyperoxia-induced animal model of BPD. MATERIAL AND METHODS The neonatal rats were exposed to 90% oxygen (O2) continuously for 14 days to mimic the BPD-like lung injury. These rats were then randomly assigned to the following four groups: in room air (air), in 90% O2, in 90% O2 with null adenovirus vector infection (O2+Ad), and in 90% O2 with gene therapy through adenovirus transfected hBD2 (O2+Ad-hBD2). Morphology of lungs, pulmonary function and expression of inflammatory cytokines on P7, P10, P14, and P21 were documented and compared across the 4 groups. RESULTS The overexpression of hBD2 mediated by the adenovirus vector was successfully constructed. hBD2 gene therapy increased hBD2 mRNA expression, increased radial alveolar count (RAC), lung volume and compliance, decreased mean linear intercept (MLI), tissue damping, and elastance. Furthermore, pro-inflammatory cytokines IL-1ß, IL-6, and TNF-alpha were inhibited and anti-inflammatory cytokines IL-10 was increased in the lungs of rats in O2+Ad-hBD2 group. CONCLUSIONS In hyperoxia-induced rat models of BPD, hBD2 promotes alveolarization and improves pulmonary function. The mechanism may contribute in alleviating inflammation response and inhibiting pro-inflammatory factors including IL-1ß, IL-6, and TNF-alpha.

Clinical characteristics of preterm ovarian hyperstimulation syndrome: seven cases from China and 14 cases from the literature.

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition with only a few reported cases. The objective of this study is to investigate the clinical characteristics of 21 POHS cases (seven from China and 14 from the literature). Suspected patients (n = 7) were referred for further confirmation and data on demographics, family history, clinical manifestations (edema developed in the vulva, the hypogastric site and the upper leg), serum and sonographic assessments (ovarian cyst/cysts, gonadotropins, and estradiol levels), the natural course of patients were documented. We did not observe substantial differences in clinical manifestations among POHS patients from China relative to that from the literature. Preterm female newborns developed edema in the vulva, the hypogastric site and the upper leg at 30-39+6 weeks of post-conception age (PCA) as the major clinical manifestations. The characteristic also included high gonadotropins and estradiol, and ovarian cysts. This condition can self-resolve. Clinical manifestations of POHS patients from China are similar to those from the literature. The pathognomonic signs of POHS include vulvar, hypogastric, and upper leg edema developed at 30-39+6 PCA along with high gonadotropins and E2 values and the presence of ovarian cysts in preterm female newborns and the syndrome can self-resolve.

Decreased topoisomerase IIα expression and altered histone and regulatory factors of topoisomerase IIα promoter in patients with chronic benzene poisoning.

Topoisomerase IIα (Topo IIα) has been implicated in the benzene-induced hemotoxicity in vitro. This study was to examine the effect of in vivo chronic benzene exposure on Topo IIα in human bone marrow mononuclear cells, and to further explore the mechanism underlying decreased Topo IIα expression in patients with chronic benzene exposure. Topo IIα activity, expression, and mRNA level assessed by DNA cleavage/relaxation assay, Western blot, and reverse transcriptase-PCR, decreased in patients with benzene exposure. These changes were accompanied by reduced histone H4 and H3 acetylation and H3K4 methylation, and increased H3K9 methylation in the Topo IIα promoter, which were evaluated by chromatin immunoprecipitation (ChIP) assay. In addition, there were alterations in mRNA levels of Topo IIα promoter regulatory factors such as SP1, ATF-2, SP3, NF-YA, NF-M, P53, C-MYB, C-JUN, and ICBP90. Our results demonstrate that Topo IIα expression was reduced in patients with chronic benzene exposure, which was accompanied by alterations in histone acetylation and methylation and regulatory factor mRNA levels of Topo IIα promoter.