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The cover shows immunofluorescence of cystic fibrosis pig gallbladder organoids. Blue, green, and gray represent DAPI, Na+/K+ ATPase, and actin, respectively. For more information, see the paper by Zarei et al, p 1388, this issue.
In this study, the authors assess the early pathogenesis of cystic fibrosis (CF) pig gallbladder disease. The CF pig gallbladder epithelium lacks cAMP-stimulated anion and fluid transport. CF pig gallbladders also demonstrate increased luminal mucins MUC5AC and MUC5B accumulation without significant changes in the epithelial expression of gel-forming mucins compared to non-CF pigs.
This study provides insight into the function of Sox13 in hepatocellular carcinoma (HCC). Sox13 serves as a key regulator of HCC cell migration, invasion, and epithelial-to-mesenchymal transition by transactivating Twist1. Sox13 forms heterodimers with Sox5 to enhance Twist1 transcriptional activity. In addition, overexpression of Sox13 indicates poor prognosis for HCC patients. These findings implicate Sox13 as a potential therapeutic target for HCC.
The authors demonstrate that cholestasis impairs hepatic lipid storage via AMP-activated protein kinase (AMPK) and CREB signaling in hepatitis B virus surface protein transgenic mice. The pharmacological modulation of AMPK and CREB signaling might be a promising therapeutic concept for the treatment of fatty liver diseases.
The authors show that exposure of neonatal mice to the toxin biliatresone creates an animal model of biliary atresia. Such mice develop clinical signs of biliary obstruction, inflammatory cell infiltration and liver fibrosis.
This study reveals that miR-185-5p alleviates endoplasmic reticulum (ER) stress, prevents epithelial dedifferentiation and subsequently improves renal fibrosis by downregulating activating transcription factor 6 (ATF6). The miR-185-5p/ATF6 pathway is proposed as a novel regulatory mechanism for renal fibrosis and may provide a therapeutic strategy for renal fibrosis associated with ER stress.
To investigate genetic homozygosity in pediatric teratomas, this study analyses 13 sacrococcygeal, 12 ovarian, and 3 testicular teratomas in children by short tandem repeat (STR) genotyping. While genetic homozygosity is frequent in adult ovarian teratomas, no evidence of genetic homozygosity is seen in patients younger than 4 years, arguing pediatric teratomas arise at an earlier stage of germ cell development.
Combination of antihypertensive drugs with NSAID analgesics may cause a syndrome called triple whammy (TW) acute kidney injury (AKI), most often in the elderly. A rat model reveals that the TW-AKI is a prerenal form of AKI, only occurring in previously dehydrated rats, a condition particularly rife among the aged.
The authors developed an in vivo model to assess patterns of peritoneal dissemination of colorectal cancer cell lines that recapitulates the high heterogeneity observed between patients. Great variation in the extent of peritoneal outgrowth, localization and clonal dynamics between cell lines was observed and a putative association with KRAS pathway activation was identified.
Liquid biopsy is a novel promising, but technically challenging tool in oncology. We compared various circulating DNA extraction and sequencing systems used within four Swiss laboratories. Results were highly congruent, with perfect sensitivity down to 1% mutation frequency. We also determined several key factors to validate when implementing such tests.
Detailed protocols for immunohistochemical and in situ hybridization assays for the detection of SARS-CoV-2 are provide so they can be readily implemented in pathology laboratories and medical examiner offices for diagnostic and research purposes. These assays were found to represent a sensitive and specific method for detecting the virus in tissue samples.