Optimizing diabetic kidney disease animal models:Insights from a meta-analytic approach

Diabetic kidney disease(DKD)is a prevalent complication of diabetes,often leading to end-stage renal disease.Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies.However,current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD.Additionally,modeling DKD is often a time-consuming,costly,and labor-intensive process.The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research.A total of 1215 articles were retrieved with the keywords of“diabetic kidney disease”and“animal experiment”in the past 10 years.Following screening,84 articles were selected for inclusion in the meta-analysis.Review manager 5.4.1 was employed to analyze the changes in blood glucose,glycosylated hemoglobin,total cholesterol,triglyceride,serum creatinine,blood urea nitrogen,and urinary albumin excretion rate in each model.Renal lesions shown in different models that were not suitable to be included in the metaanalysis were also extensively discussed.The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations.In conclusion,our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.

Chuanxiong Rhizoma extracts prevent liver fibrosis via targeting CTCF-c-MYC-H19 pathway

Objective:Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases.Chuanxiong Rhizoma(Chuanxiong in Chinese,CX)is a traditional Chinese herbal product to prevent cerebrovascular,gynecologic and hepatic diseases.Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells(HSCs).Here,this study aimed to compare the protection of different CX extracts on bile duct ligation(BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.Methods:The active compounds of CX extracts were identified by high performance liquid chromatography(HPLC).Network pharmacology was used to determine potential targets of CX against hepatic fibrosis.Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation.The expression of targets of interest was determined by quantitative real-time PCR(qPCR)and Western blot.Results:Different CX extracts were identified by tetramethylpyrazine,ferulic acid and senkyunolide A.Based on the network pharmacological analysis,42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis.Different aqueous,alkaloid and phthalide extracts of CX(CX_(AE),CX_(AL) and CXP_(HL))significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor(CTCF)-c-MYC-long non-coding RNA H19(H19)pathway in the BDL-induced mouse model.Meanwhile,CX extracts,especially CX_(AL) and CX_(PHL) also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid(TCA),lithocholic acid(LCA)and transforming growth factor beta(TGF-β),as illustrated by decreased bile duct proliferation markers.Conclusion:Our data supported that different CX extracts,especially CX_(AL) and CX_(PHL) significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway,providing novel insights into the anti-fibrotic mechanism of CX.

Chromosome-Level Reference Genome and Population Genomic Analysis Provide Insights into the Evolution and Improvement of Domesticated Mulberry (Morns alba)

Mulberry(Morns spp.)is the sole plant consumed by the domesticated silkworm.However,the genome of domesticated mulberry has not yet been sequenced,and the ploidy level of this species remains unclear.Here,we report a high-quality,chromosome-level domesticated mulberry(Morus alba)genome.Analysis of genomic data and karyotype analyses confirmed that M.alba is a diploid with 28 chromosomes(2/7=2x=28).Population genomic analysis based on resequencing of 134 mulberry accessions classified domesticated mulberry into three geographical groups,namely,Taihu Basin of southeastern China(Hu mulberry),northern and southwestern China,and Japan.Hu mulberry had the lowest nucleotide diversity among these accessions and demonstrated obvious signatures of selection associated with environmental adaptation.Further phylogenetic analysis supports a previous proposal that multiple domesticated mulberry accessions previously classified as different species actually belong to one species.This study expands our understanding of genome evolution of the genus Morus and population structure of domesticated mulberry,which would facilitate mulberry breeding and improvement.