As a chronic metabolic disease caused by disorders of purine metabolism, gout has shown increasing incidence rate worldwide. Considering that gout is not easily treated and cured, further studies are explored to prevent gout development through diet modification. Both β-carotin and green tea powder are rich in dietary fiber, which helps maintain the balance of gut microbiota in humans. The aim of this study was to investigate the effects of β-carotin and green tea powder diet on the prevention of gouty arthritis in relation to the bacterial structure of gut microbiota in mice. We successfully induced gouty arthritis in C57BL/6 mice by injecting monosodium urate (MSU) crystals and feeding high-fat diet (HFD), and further investigated the effects of additional β-carotin and green tea powder in the diets of mice on the prevention of gouty arthritis in mice. Our results showed that diet of β-carotin and green tea powder reduced the joint swelling and pain in mice with gout, reduced the levels of serum uric acid (UA) and three types of pro-inflammatory cytokines, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), improved the gut microbiota profile, and reduced the metabolic levels of purines and pyrimidines. In conclusion, our study provided evidence to support the application of β-carotin and green tea powder diet as a dietary adjustment method to prevent and treat gouty arthritis.

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Background. Nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) is an uncommon form of hearing loss (HL) that typically affects frequencies at 2000 Hz and below. Heterozygous variants in the WFS1 gene at the DFNA6/14/38 locus are considered a common cause of LFSNHL. To date, 34 different pathogenic genetic variants have been reported to cause LFSNHL with seven of these variants identified in the Chinese population. However, limited reports are available on the association between WFS1 gene and LFSNHL. Here, we report a five-generation Chinese family with an autosomal dominant inheritance pattern of postlingual and progressive LFSNHL. Methods. Routine clinical and audiological examinations were performed on 16 affected and 7 healthy members in this family. The targeted next-generation sequencing of 127 known deafness genes was performed to identify variants in affected individuals. Sanger sequencing were further employed to confirm the pathogenic variant identified. Results. A novel heterozygous pathogenic genetic variant c.2530G > T (p.Ala844Ser) was identified in the WFS1 gene in all patients of this family. The mutated Ala residue is evolutionarily conserved and cosegregated with HL. The variant was predicted to be deleterious by MutationTaster, PolyPhen-2, LRT, and Fathmm software. Conservation analysis and 3D protein structure model indicated that the variant caused a structural change in the protein. Conclusions. Our present study identifies a novel heterozygous WFS1 variant associated with LFSNHL in a Chinese family.

BackgroundMutations in lipoxygenase homology domain 1 (LOXHD1) cause autosomal recessive inheritance, leading to high-frequency and intermediate-frequency hearing losses in patients. To date, studies on the localization of LOXHD1 gene expression are limited. In this study, we aimed to observe the expressions of Loxhd1b in zebrafish, C57BL/6 murine cochlea, and HEI-OC1 cells.MethodsThe expression of Loxhd1b in the auditory system of zebrafish was explored by in situ hybridization experiments of zebrafish embryos. The expression of Loxhd1b in cochlear and HEI-OC1 cells of C57BL/6 mice was analyzed by immunofluorescence staining. Confocal microscopic in vivo imaging was used to detect the number and morphological characteristics of lateral line neuromasts and inner ear hair cells in zebrafish that knocked down Loxhd1b gene. The effect of knockdown Loxhd1b gene on the development of zebrafish otolith and semicircular canal was observed using microscopic. Transcriptome sequencing was used to identify downstream molecules and associated signaling pathways and validated by western blotting, immunostaining, and rescue experiments.ResultsResults of the in situ hybridization with zebrafish embryos at different time points showed that Loxhd1b was expressed in zebrafish at the inner ear and olfactory pores, while the immunostaining showed that Loxhd1 was expressed in both C57BL/6 mouse cochlea and HEI-OC1 cells. Loxhd1b knockdown causes a decrease in the number of spinal and lateral line neuromasts in the inner ear of zebrafish, accompanied by weakened hearing function, and also leads to developmental defects of otoliths and ear follicles. The results of transcriptomics analysis revealed the downstream molecule brain-derived neurotrophic factor (BDNF) and verified that Loxhd1b and BDNF regulate the formation of zebrafish hair cells by synergistic regulation of BDNF/TrkB/ERK pathway based on western blotting, immunostaining, and rescue experiments.ConclusionThis was the first time that the BDNF/TrkB/ERK pathway was identified to play a critical role in the molecular regulation of the development of zebrafish hair cells and the auditory development by Loxhd1b.