Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

[Clinical features and genetic analysis of two children with Williams-Beuren syndrome].

OBJECTIVE: To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). METHODS: Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. RESULTS: Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3；PM2_Supporting). CONCLUSION: Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.

MicroRNA-485-3p Promotes the Inflammatory Response and Extracellular Matrix Deposition by Activating Wnt/ß-Catenin Signaling in Human Airway Smooth Muscle Cells.

The aim of this study was to study the effects of microRNA (miR)-485-3p on the inflammatory response and extracellular matrix deposition of human airway smooth muscle cells (HASMCs). The levels of miR-485-3p and WIF1 in peripheral blood of pediatric asthma (PA) patients and controls were examined by quantitative real-time polymerase chain reaction (qRT-PCR). miR-485-3p inhibitor and mimic, together with negative control (NC) inhibitor/ mimic, were transfected into HASMCs treated with tumor necrosis factor (TNF)-α. The levels of eotaxin, interleukin (IL)-8, and IL-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). Cellular immunofluorescence analysis of fibronectin was also performed. The target genes of miR-485-3p were predicted and validated using TargetScan and dual-luciferase reporter gene assay. The protein levels of IL-6, eotaxin, IL-8, collagen III, collagen I, MMP-9, TIMP-1, MMP-2, axin, ß-catenin, phosphorylated ß-catenin, GSK3ß, p-GSK3ß, and WIF1 were tested by Western blot. The level of miR-485-3p was increased, whereas expression of WIF1 was low in PA patients. In TNF-α-induced HASMCs, miR-485-3p overexpression promoted the inflammatory response and the accumulation of extracellular matrix. WIF1 was a direct target of miR-485-3p. Silencing miR-485-3p inhibited activation of Wnt/ß-catenin signaling. The reductions in the inflammatory response and ECM accumulation caused by silencing miR-485-3p were induced by blocking Wnt/ß-catenin signaling. Thus, miRNA-485-3p targets WIF1 and activates Wnt/ß-catenin signaling, facilitating activation of the inflammatory response and ECM accumulation in HASMCs.

Pollen allergens sensitization characteristics and risk factors among allergy rhinitis of children in mainland China: A multicenter study.

Background: No comprehensive multicenter study of sensitization patterns among patients with allergic rhinitis (AR) to various common pollen allergens was available nationwide, and risks factors of pollen-induced allergic rhinitis (PiAR) in mainland China was unclear. This study aimed to fill this gap. Methods: A multicenter study was performed on 736 AR patients aged below 18 from four regions of mainland China. Patients completed a standardized questionnaire asking for the environmental risk factors and AR severity, and undertook skin prick tests (SPT) with 14 common pollen allergens. Findings: Among the 736 patients, 341 patients (46.33%) suffered at least one positive pollen allergen sensitization. The positive rate of pollen allergens was significantly higher in the high-age group (Damato et al., 2007; Wang et al., 2018; Luo et al., 2016; Demoly et al., 2011; Sampson and Albergo, 1984; Li et al., 2009; Luo et al., 2021; Ziska and Beggs, 2011; Melén et al., 2020; Jensen-Jarolim, 2017; Rönmark et al., 2017; Ge et al., 2017) [6-17] than the low-age group ( ≤ 5), while no significant difference was found between the sexes. The sensitizations to pollen allergens varied widely among four geographical areas. The positive rate was higher in north China and west China than in east China, and south China had the lowest positive rate. The region of residence, ages, ethnic minorities, history of pollen exposure, the material of living room floor and material of pillow were statistically significant risks of PiAR. Interpretation: This study provides new insights into the pollen allergens sensitization characteristics in AR and the factors affecting PiAR in mainland China.

The Role of RAD6B and PEDF in Retinal Degeneration.

RAD6B is an E2 ubiquitin-conjugating enzyme, playing an important role in DNA damage repair, gene expression, senescence, apoptosis and protein degradation. However, the specific mechanism between ubiquitin and retinal degeneration requires more investigation. Pigment epithelium-derived factor (PEDF) has a potent neurotrophic effect on the retina, protecting retinal neurons and photoreceptors from cell death caused by pathological damage. In this study, we found that loss of RAD6B leads to retinal degeneration in mice, especially in old age. Affymetrix microarray analysis showed that the PEDF signal was changed in RAD6B deficient groups. The expression of γ-H2AX, ß-Gal, P53, Caspase-3, P21 and P16 was increased significantly in retinas of RAD6B knockout (KO) mice. Our studies suggest that RAD6B and PEDF play an important role in the health of retina, whereas the absence of RAD6B accelerates the degeneration.

A Multicenter Study Assessing Risk Factors and Aeroallergens Sensitization Characteristics in Children with Self-Reported Allergic Rhinitis in China.

BACKGROUND: Up to now, epidemiological studies on allergy rhinitis (AR) have primarily focused on determining the risk of disease in Chinese adults, with the majority of them designed by single centers, while cross-sectional and epidemiological data describing allergic sensitization in children with self-reported AR are scarce. OBJECTIVE: This study was estimating of the latest information about the sensitization patterns and risk factors of clinical AR to develop effective strategies for the prevention and treatment of AR. METHODS: We conducted a cross-sectional survey between January 2020 and June 2021 involving children from seven cities in China who reported AR. A total of 762 children participated in this survey. To evaluate the risk factors and specific sensitization patterns of clinical AR through questionnaires and specific immunoglobulin E to 11 aeroallergens. RESULTS: Of the 762 patients, 593 (77.8%) had at least one positive IgE level. Aged 7-14 years (OR 1.503, (95% CI 1.058-2.136), P = 0.023); With allergic conjunctivitis (OR 1.843, (95% CI 1.297-2.620), P = 0.001) and living in the Eastern (OR 1.802, (95% CI 1.263-2.573), P = 0.001) all elevated the risk of clinical AR associated with aeroallergens. The sensitization rates of D. pteronyssinus and D. farinae were higher than those of other allergens in the 0-6 and 7-14 years old age groups. The most common aeroallergens among self-reported children with AR in the eastern were D. farinae (74.9%) and D. pteronyssinus (74.3%), while in the western were mugwort (60.0%) and marguerite (56.6%). Majority of sIgE-positive subjects were sensitized to three or more of the tested pollen allergens in the Western (52.1%), compared with 5.7% in the Eastern. CONCLUSION: There was an apparent geographic variation in childhood allergies in China. Age factors also had strong impacts on the allergen sensitization rate of children, but these impacts differed across regions.

A 10-year retrospective comparative analysis of the clinical features of brucellosis in children and adults.

INTRODUCTION: Brucellosis is a zoonosis with a wide spectrum of clinical manifestations. However, it is still unclear whether the clinical manifestations in children are significantly different from those in adults. METHODOLOGY: Patients with brucellosis and treated at the General Hospital of Ningxia Medical University between 2009 and 2019 were divided into two groups; children (88) and adults (354). Thereafter, the records of the two groups were analyzed retrospectively. RESULTS: The findings showed that: 1. School-age children, young and middle-aged individuals were more likely to suffer from brucellosis and most were male; 2. Fever and arthralgia were the most common manifestations in the two groups. In addition, fatigue and low back pain were rare in children although fever and lymphadenopathy were more common in this group. However, hepatomegaly and splenomegaly were common in both groups; 3. The most common complication was osteoarthritis and peripheral arthritis occurred more frequently in children. On the other hand, spondylitis was the most common in adults (this particularly involved the lumbar and sacral vertebrae); 4. An increase in the erythrocyte sedimentation rate, levels of the C-reactive protein and liver enzymes was common in both two groups; 5. There was no significant difference in the positive rate of the standard agglutination test between children (96.59%) and adults (95.20%). However, the positive rate of blood culture was higher in children (65.85%) than in adults (51.00%). CONCLUSIONS: Brucellosis causes damage to multiple systems and differences in clinical characteristics were found between children and adults.

Study on the Diversity of Fungal and Bacterial Communities in Continuous Cropping Fields of Chinese Chives (Allium tuberosum).

In this study, high-throughput sequencing technology was used to analyse the diversity and composition of fungal and bacterial communities in continuous cropping soil of Chinese chives. The soil nutrient was also measured to explore the rationality of current fertilization management. These results can provide a basis for the prevention and control of the continuous cropping obstacles of Chinese chives and further scientific management. Soil samples from fields continuously cropped with Chinese chives for one year, three years, and five years were collected and analysed. The results showed that the nutrient content of TP, AP, AK and TK increased significantly with increasing continuous cropping years. Short-term continuous cropping soil nutrients have not deteriorated. Alpha-diversity analysis showed that significant differences were not found in the diversity of the fungal and bacterial community among different years. Ascomycota, Basidiomycota and Mortierellomycota were the three most dominant fungal phyla. Proteobacteria, Actinobacteria, Chloroflexi and Acidobacteria were the dominant bacterial phyla. Continuous cropping makes Fusarium increase, and the beneficial bacteria Pseudomonas decreased significantly. According to the correlation heat map analysis of environmental factors, excessive phosphorus may lead to the increase of Fusarium, potassium may promote the proliferation of beneficial bacteria in the continuous cropping process, and it is necessary to regulate the application of phosphate and potassium fertilizer.

The variability of bacterial communities in both the endosphere and ectosphere of different niches in Chinese chives (Allium tuberosum).

Deciphering the various types of interactions between plants and their microbiomes is a hot topic for research in ecology as well as in plant sciences and agronomy. To analyse and compare the differences in microbial communities in different compartments of Chinese chives, high-throughput sequencing technology was employed to amplify and sequence the V5-V6 region of the 16S rDNA of microorganisms in the leaves, phylloplanes, stems, roots and rhizospheres of Chinese chives. The sequences were clustered by operational taxonomic units (OTUs), and the community composition of bacteria between the endosphere (inner tissues) and ectosphere (outer surfaces) of Chinese chives was analysed based on the OTU. Overall, the results indicated that the endophytic bacteria in Chinese chives mainly include Proteobacteria, Actinobacteria, and Actinomycetes. Alpha diversity index analysis and OTU number analysis showed that the bacterial diversity and richness of the underground plant compartments were higher than those of the above-ground parts. PCoA based on the OTU level showed that the vertical stratification structure of plants and compartments had significant effects on the bacterial community structure. The richness of endophytic bacteria also varied greatly among the different varieties of Chinese chive. A considerable number of endophytic bacteria form symbiotic and mutually beneficial relationships with host plants, which play an important role in regulating host growth, metabolism and stress resistance. Further investigations are needed to uncover the evolution of interactions between plants and endophytes.