Consequences of exposure to famine exposure on the later life eGFR decline among survivors of the Great Chinese Famine: a retrospective study.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) significantly contributes to the socio-economic burden both in China and worldwide. Previous research has shown that experiencing childhood famine is linked to various chronic conditions like diabetes, hypertension, and proteinuria. However, the long-term effects of early life famine exposure on adult kidney function remain unclear. This study investigates whether exposure to the Chinese Great Famine (1959-1962) is associated with a decline in glomerular filtration rate (GFR) later in life. MATERIALS AND METHODS: CHARLS is a population-based observational study. We analyzed data from 8,828 participants in the 2011-2012 baseline survey, updated in 2014. Participants were categorized based on their birth year into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/adult-exposed (1912-1948), and non-exposed (1963-1989) groups. The estimated GFR (eGFR) was calculated using the CKD-EPI-Cr-Cys equation (2021), with CKD defined as an eGFR below 60 mL/min/1.73 m2. RESULTS: Average eGFR values were 103.0, 96.8, 91.2, and 76.3 mL/min/1.73 m2 for the fetal-exposed, childhood-exposed, adolescence/adult-exposed, and non-exposed groups, respectively. The eGFR in the exposed groups was significantly lower compared to the non-exposed group. Specifically, famine exposure correlated with a lower eGFR (CE -9.14, 95%CI -9.46, -8.82), with the strongest association observed in the adolescence/adult-exposed group (CE -26.74, 95%CI -27.75, -25.74). Adjusting for variables such as demographics, physical and laboratory tests, complications, and personal habits like smoking and drinking did not qualitatively alter this association (CE -1.38, 95%CI -1.72, -1.04). Further stratification by sex, body mass index (BMI), alcohol consumption history, hypertension, diabetes, CESD score, and education level showed that the association remained consistent. CONCLUSIONS: Exposure to famine during different life stages can have enduring effects on GFR decline in humans.

Gene-Based Network Analysis Reveals Prognostic Biomarkers Implicated in Diabetic Tubulointerstitial Injury.

Background: Diabetic nephropathy (DN), a significant cause of chronic kidney disease (CKD), is a devastating disease worldwide. Objective: The aim of this study was to reveal crucial genes closely linked to the molecular mechanism of tubulointerstitial injury in DN. Methods: The Gene Expression Omnibus (GEO) database was used to download the datasets. Based on this, a weighted gene coexpression network analysis (WGCNA) network was constructed to detect DN-related modules and hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments were performed on the selected hub genes and modules. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed on the obtained gene signature. Results: The WGCNA network was constructed based on 3019 genes, and nine gene coexpression modules were generated. A total of 57 genes, including 34 genes in the magenta module and 23 genes in the purple module, were adapted as hub genes. 61 significantly downregulated and 119 upregulated genes were screened as differentially expressed genes (DEGs). 25 overlapping genes between hub genes chosen from WGCNA and DEG were identified. Through LASSO analysis, a 9-gene signature may be a potential prognostic biomarker for DN. To further explore the potential mechanism of DN, the different immune cell infiltrations between tubulointerstitial samples of DN and healthy samples were estimated. Conclusions: This bioinformatics study identified CX3CR1, HRG, LTF, TUBA1A, GADD45B, PDK4, CLIC5, NDNF, and SOCS2 as candidate biomarkers for the diagnosis of DN. Moreover, DN tends to own a higher proportion of memory B cell.

Homoepiboxidines: further potent agonists for nicotinic receptors.

Homoepiboxidine (3) and the corresponding N-methyl (4) and N-benzyl (5) derivatives were prepared from a 6beta-carbomethoxynortropane (8). Affinities and functional activities at neuromuscular, central neuronal and ganglionic-type nicotinic receptors were compared to those of epibatidine 1, and epiboxidine 2. Homoepiboxidine had equivalent affinity/activity to epiboxidine at neuromuscular, neuronal alpha4beta2, and most alpha3-containing ganglionic-type nicotinic receptors. The N-substituted derivatives showed reduced affinity/activity at most receptor subtypes. Replacement of the methylisoxazole moiety of 3 and 4 with a methyloxadiazole moiety provided analogues 6 and 7, which had greatly reduced affinity/activity in virtually all assays at nicotinic receptors. Marked analgetic activity in mice occurred at the following ip doses: epibatidine 10 microg/kg; epiboxidine 25 microg/kg; homoepiboxidine 100 microg/kg; N-methylhomoepiboxidine 100 microg/kg; the methyloxadiazole (6) 100 microg/kg. The time course at such ip doses was significantly longer for homoepiboxidine 3 with marked analgesia still manifest at 30 min post-injection. Epiboxidine and the homoepiboxidines were less toxic than epibatidine.