Established the first clinical prediction model regarding the risk of hyperuricemia in adult IgA nephropathy.

OBJECTIVE: To construct a novel nomogram model that predicts the risk of hyperuricemia incidence in IgA nephropathy (IgAN). METHODS: Demographic and clinicopathological characteristics of 1184 IgAN patients in the First Affiliated Hospital of Zhengzhou University Hospital were collected. Univariate analysis and multivariate logistic regression were used to screen out hyperuricemia risk factors. The risk factors were used to establish a predictive nomogram model. The performance of the nomogram model was evaluated using an area under the receiver-operating characteristic curve (AUC), calibration plots, and a decision curve analysis. RESULTS: Independent predictors for hyperuricemia incidence risk included sex, hypoalbuminemia, hypertriglyceridemia, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24 h TP), gross hematuria and tubular atrophy/interstitial fibrosis (T). The nomogram model exhibited moderate prediction ability with an AUC of 0.834 (95% CI 0.804-0.864). The AUC from validation reached 0.787 (95% CI 0.736-0.839). The decision curve analysis displayed that the hyperuricemia risk nomogram was clinically applicable. CONCLUSION: Our novel and simple nomogram containing 8 factors may be useful in predicting hyperuricemia incidence risk in IgAN.

Expression Analysis of Lanosterol Synthase Gene in Dynamic Accumulation of Triterpenoids in Sanghuangporus baumii.

BACKGROUND: Sanghuangporus baumii is a traditional Chinese medicine with anti- cancer, anti-tumor, and anti-inflammatory effects. Triterpenoids are one of the main medicinal ingredients found in S. baumii. However, the dynamic changes of triterpenoids content and its molecular regulation mechanism are still unclear. OBJECTIVE: Some studies have shown that Lanosterol synthase ( LS) is a key enzyme involved in the mevalonate pathway (MVA pathway) to produce lanosterol, which is a precursor for synthesizing S. baumii triterpenoids. Therefore, the study of LS gene and expression characteristics can provide clues for the further study of triterpenoids synthesis. METHODS: The PCR, RACE PCR, RT-PCR, homologous recombination and prokaryotic expression technology were used to research the gene characteristic and dynamic changes of LS transcription level. RESULTS: The S. baumii LS sequence included a 5'-untranslated region (129 bp), a 3'-untranslated region (87 bp), and an open reading frame (2,229 bp) encoding 734 amino acids. The S. baumii LS protein was expressed in E. coli BL21 (DE3). The transcription start site of the S. baumii LS promoter sequence ranged from 1 740 bp to 1790 bp. The LS promoter contained 12 CAAT-boxes, 5 ABREs, 6 G-Boxes, 6 CGTCA-motifs, and so on. The LS transcription levels were the highest on day 11 in mycelia (1.6-fold), and the triterpenoids content also gradually increased. The transcription levels began to decrease on day 13, but the triterpenoids content still increased. CONCLUSION: The S. baumii LS was cloned and characterized to help to understand the mechanism of triterpenoids synthesis. In addition, we studied the relationship between LS transcription level and triterpenoid dynamic accumulation, and we found that they had a certain correlation.

Hyperuricemia aggravates the progression of IgA nephropathy.

OBJECTIVE: The relationship between hyperuricemia and IgA nephropathy (IgAN) was evaluated systematically in this research. METHODS: The Preferred Reporting Items for Systematic Review and Meta-analysis statement was employed to design and report the study. RESULTS: Twenty-five studies were included in this meta-analysis with a total of 6048 IgAN patients. The clinical indicators indicated that blood urea nitrogen (BUN) (p < 0.00001, mean difference (MD) = 2.60, 95% confidence interval (CI) 1.74-3.46), serum creatinine (Scr) (p < 0.00001, MD = 44.56, 95% CI 31.15-57.98), diastolic blood pressure(DBP) (p < 0.00001, MD = 3.86, 95% CI 2.84-4.88), systolic blood pressure(SBP) (p < 0.00001, MD = 6.71, 95% CI 4.70-8.71), and 24-h urine protein(24 h TP) (p < 0.00001, MD = 0.76, 95% CI 0.58-0.94) were significantly increased in IgAN with hyperuricemia group than that in normouricemic IgAN group. The pathological analysis indicated that mesangial proliferation (p < 0.00001, MD = 0.12, 95% CI 0.07-0.17), vascular lesion (p < 0.00001, MD = 0.17, 95% CI 0.13-0.20), segmental lesion (p < 0.00001, MD = 0.15, 95% CI 0.03-0.26), tubulointerstitial damage (p < 0.00001, MD = 1.27, 95% CI 1.06-1.48), and glomerulosclerosis (p < 0.00001, MD = 0.56, 95% CI 0.40-0.72) were considerably climbed in IgAN patients with hyperuricemia compared without hyperuricemia group. Additionally, the estimated glomerular filtration rate (p < 0.00001, MD = - 29.03, 95% CI - 36.83 to - 21.23) was decreased in IgAN patients with hyperuricemia compared with normouricemic group. CONCLUSION: Hyperuricemia exacerbates IgAN prognosis through aggravating the clinical outcomes and pathological results of IgAN.

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1.

The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance.

Genetic and Epigenetic Diversities Shed Light on Domestication of Cultivated Ginseng (Panax ginseng).

Chinese ginseng (Panax ginseng) is a medically important herb within Panax and has crucial cultural values in East Asia. As the symbol of traditional Chinese medicine, Chinese ginseng has been used as a herbal remedy to restore stamina and capacity in East Asia for thousands of years. To address the evolutionary origin and domestication history of cultivated ginseng, we employed multiple molecular approaches to investigate the genetic structures of cultivated and wild ginseng across their distribution ranges in northeastern Asia. Phylogenetic and population genetic analyses revealed that the four cultivated ginseng landraces, COMMON, BIANTIAO, SHIZHU, and GAOLI (also known as Korean ginseng), were not domesticated independently and Fusong Town is likely one of the primary domestication centers. In addition, our results from population genetic and epigenetic analyses demonstrated that cultivated ginseng maintained high levels of genetic and epigenetic diversity, but showed distinct cytosine methylation patterns compared with wild ginseng. The patterns of genetic and epigenetic variation revealed by this study have shed light on the domestication history of cultivated ginseng, which may serve as a framework for future genetic improvements.