bims-raghud 2026-05-24 papers

Issue of 2026–05–24
three papers selected by
Irene Sambri, TIGEM

Int J Biol Sci. 2026 ;22(9): 4806-4825

Zebrafish in Cardiovascular Disease Research: from Model to Application.

Ranran Wang, Qian Zhang, Shuhui Zhang, Ziyan Wang, Zongyuan Zhou, Tianyi Yuan, Bo Zhang.

Cardiovascular diseases (CVDs) remain a major cause of global morbidity and mortality, yet their complex pathophysiology is difficult to recapitulate in conventional mammalian models fully. Compared with traditional mammalian and in vitro systems, zebrafish offer several distinct advantages for CVD research. Their small size, high fecundity, and rapid development make them particularly suitable for high-throughput screening, while embryonic transparency enables real-time, noninvasive imaging of dynamic cardiac processes. High genetic homology with humans, together with facile genetic manipulation, further supports their utility in modeling cardiovascular disorders. In addition, their unique capacity for cardiac regeneration provides a valuable platform for regeneration studies. A wide range of endogenous and exogenous zebrafish models have successfully recapitulated key features of human CVDs, thereby facilitating mechanistic investigation and the identification of critical signaling pathways. Zebrafish also enable cost-efficient phenotypic screening and have contributed substantially to early-stage drug discovery and cardiotoxicity assessment. In summary, despite anatomical differences from mammals, zebrafish combine genetic tractability, phenotypic fidelity, and screening efficiency, underscoring their value in advancing drug discovery and therapeutic development for CVDs.

Keywords: Cardiovascular disease; Disease modeling; Drug discovery; Heart; High-throughput screening; Zebrafish

DOI: https://doi.org/10.7150/ijbs.131893

Nephron. 2026 May 18. 1-24

Human kidney organoids to uncover preterm birth-associated low nephron endowment.

Bartholomeus T van den Berge, Bart Smeets, Michiel F Schreuder, Jitske Jansen.

Preterm birth disrupts kidney development, resulting in reduced nephron number and structural immaturity of glomeruli and podocytes that increases the risk of hypertension, proteinuria, and subsequently chronic kidney disease (CKD) later in life. Since nephrogenesis ceases around 36 weeks of gestation, preterm infants cannot generate new nephrons after birth, making them vulnerable to long-term renal dysfunction. Unravelling the mechanisms behind this impaired development has been limited by the complexity of human nephrogenesis and the lack of physiologically relevant experimental models. Recent advances in human induced pluripotent stem cell-derived kidney organoids have made it possible to model nephrogenesis in vitro. These organoids replicate key processes such as nephron differentiation, ureteric bud branching, and kidney vascularization, allowing detailed study of kidney development and injury. Moreover, molecular interventions-including retinoic acid (RA), glial-cell-line-derived neurotrophic factor (GDNF), and insulin-like growth factor 1 (IGF1)-show the potential to enhance nephron formation and protect against kidney injury. Key Messages • Kidney organoids provide a powerful, human-relevant system to study nephrogenesis and CKD mechanisms. • Integration of the ureteric bud and enhanced vascularization significantly improves organoid maturity towards a more in vivo-like state. • Targeted molecular interventions such as RA, GDNF, and IGF1 offer potential strategies to enhance nephron endowment and mitigate CKD risk in preterm-born individuals, and may be studied using kidney organoids.

DOI: https://doi.org/10.1159/000552561

Virchows Arch. 2026 May 21.

Clinicopathologic characterization of renal tumors with Folliculin (FLCN) biallelic inactivation.

Stephanie E Siegmund, Sara E Wobker, Lara R Harik, Maria Tretiakova, Shivani Kandukuri, Kiril Trpkov, Fiona Maclean, Igor Odintsov, Michel Alchoueiry, Manju Aron, Maria M Picken, Jonathon Mahlow, Adebowale J Adeniran, Peter A Humphrey, Holger Moch, Harrison Tsai, Elizabeth P Henske, Michelle S Hirsch.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder caused by germline inactivation of the folliculin gene (FLCN). Approximately 25% of BHD syndrome patients are diagnosed with renal tumors, which can be multifocal and/or bilateral. These tumors have been reported to span a broad histologic spectrum; however, the majority exhibit a distinctive histology characterized by intermingled cytologic features similar to that seen in oncocytoma and chromophobe renal cell carcinoma. Accordingly, such tumors were previously termed 'hybrid oncocytic chromophobe tumor' (HOCT). To date, most studies have characterized tumors arising in BHD syndrome patients without molecular confirmation of FLCN biallelic inactivation; accordingly, the clinicopathologic characterization of molecularly confirmed FLCN biallelic inactivated tumors remains limited. This study evaluates a multi-institutional cohort of 18 renal tumors from different individuals, including integrated histologic, immunohistochemical, and targeted next-generation sequencing analyses. While all patients exhibited clinical characteristics raising suspicion for BHD syndrome, germline status was not available in 5 patients. Nevertheless, molecular analysis demonstrated findings supportive of FLCN biallelic inactivation in all patients, and there were no other candidate driver alterations or recurrent molecular findings. Histologically, most tumors showed 'conventional' histology consisting of solid or nested growth with a characteristic mosaic population of eosinophilic and clear cells and low-grade nuclear features, including frequent perinuclear halos and binucleation. Two cases showed 'non-conventional' histology including tubulocystic and tubulopapillary architecture. Immunohistochemistry revealed consistent GPNMB expression and a distinctive mosaic staining pattern for KRT7, L1CAM, and GATA3, aiding distinction from other eosinophilic renal neoplasms. Follow-up was available for 17 patients (median 37 months, range 1-110 months). Both patients with non-conventional morphology demonstrated advanced stage at presentation, including one with metastatic disease. Collectively, these findings define one of the largest molecularly-confirmed cohorts of FLCN biallelic inactivated tumors to date and support recognition of FLCN-driven tumors as a distinct, molecularly defined entity.

Keywords: Biallelic inactivation; Birt Hogg Dube; Folliculin (FLCN); GPNMB; Immunohistochemistry; Kidney; Next generation sequencing; Renal

DOI: https://doi.org/10.1007/s00428-026-04588-x