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Genes of UMOD, HNF1B, MUC1, REN and SEC61A1 were reported to be associated with autosomal dominant tubulointerstitial kidney disease (ADTKD). 48 probands and their family members (N = 27) were enrolled in this genetic screening study. A combination of methods was employed for comprehensive molecular analysis of both copy number variations (CNVs) and single nucleotide variants (SNVs). 35 probands were followed for years. The phenotype-genotype and genotype-outcome correlation were inferred from these datasets. In this cohort, 18 probands were diagnosed with ADTKD, according to Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Moreover, 11 probands were diagnosed with ADTKD-UMOD, one with ADTKD-REN and one with ADTKD-HNF1B, based on molecularly confirmed pathogenic variants. The 11 UMOD variants were mainly located in codons 28 to 289 and half of the variants were found to change the cysteine amino acid. According to the follow-up data, suspected ADTKD individuals had a better prognosis compared to ADTKD individuals (p = 0.029). Individuals with a cysteine substitution in the UMOD gene appeared to have a better prognosis than individuals with other amino acid substitutions (p = 0.015). [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new diagnostic criterion based on hepatic steatosis and metabolic dysfunction. However, a comprehensive evaluation of the association of MAFLD dynamic transitions with arterial stiffness progression has yet to be conducted. This cohort study included 8807 Chinese health check-up participants (median follow-up = 50.2 months). Participants were categorized into four groups according to MAFLD status at baseline and follow-up (none, persistent, developed and regressed). Arterial stiffness progression was assessed by the annual brachial-ankle pulse wave velocity (ba-PWV) increase and arterial stiffness incidence. Compared with the non-MAFLD group, the annual increase in ba-PWV was highest in the persistent-MAFLD group [6.75 cm/s/year, (95% CI 4.03–9.33)], followed by the developed—[6.35 cm/s/year, (95% CI 3.80–8.91)] and the regressed—[1.27 cm/s/year, (95% CI − 2.18 to 4.72)] MAFLD groups. Similarly, compared with the non-MAFLD group, the persistent-MAFLD group had a 1.31-fold increased arterial stiffness risk [OR 1.31; 95% CI 1.03–1.66]. The associations of MAFLD transition patterns with arterial stiffness incidence did not differ across any clinically specific subgroups evaluated. Furthermore, the potential effect of dynamic changes in cardiometabolic risk factors on arterial stiffness incidence among persistent-MAFLD participants was mostly driven by annual fasting glucose and triglyceride increases. In conclusion, persistent MAFLD was associated with an increased risk of arterial stiffness development. Moreover, in persistent-MAFLD subjects, elevated blood glucose and triglyceride levels might facilitate the arterial stiffness incidence. [ABSTRACT FROM AUTHOR]

Exposure to cigarette smoke (CS) results in injury to the epithelial cells of the human respiratory tract and has been implicated as a causative factor in the development of chronic obstructive pulmonary disease and lung cancers. The application of omics-scale methodologies has improved the capacity to understand cellular signaling processes underlying response to CS exposure. We report here the development of an algorithm based on quantitative assessment of transcriptomic profiles and signaling pathway perturbation analysis (SPPA) of human bronchial epithelial cells (HBEC) exposed to the toxic components present in CS. HBEC were exposed to CS of different compositions and for different durations using an ISO3308 smoking regime and the impact of exposure was monitored in 2263 signaling pathways in the cell to generate a total effect score that reflects the quantitative degree of impact of external stimuli on the cells. These findings support the conclusion that the SPPA algorithm provides an objective, systematic, sensitive means to evaluate the biological impact of exposures to CS of different compositions making a powerful comparative tool for commercial product evaluation and potentially for other known or potentially toxic environmental smoke substances. [ABSTRACT FROM AUTHOR]

Osmoregulation and osmoconformation are two mechanisms through which aquatic animals adapt to salinity fluctuations. The euryhaline crab Scylla paramamosain, being both an osmoconformer and osmoregulator, is an excellent model organism to investigate salinity adaptation mechanisms in brachyurans. In the present study, we used transcriptomic and proteomic approaches to investigate the response of S. paramamosain to salinity stress. Crabs were transferred from a salinity of 25 ppt to salinities of 5 ppt or 33 ppt for 6 h and 10 days. Data from both approaches revealed that exposure to 5 ppt resulted in upregulation of ion transport and energy metabolism associated genes. Notably, acclimation to low salinity was associated with early changes in gene expression for signal transduction and stress response. In contrast, exposure to 33 ppt resulted in upregulation of genes related to amino acid metabolism, and amino acid transport genes were upregulated only at the early stage of acclimation to this salinity. Our study reveals contrasting mechanisms underlying osmoregulation and osmoconformation within the salinity range of 5–33 ppt in the mud crab, and provides novel candidate genes for osmotic signal transduction, thereby providing insights on understanding the salinity adaptation mechanisms of brachyuran crabs. [ABSTRACT FROM AUTHOR]