Pathology

Dynamics of compartment-specific proteomic landscapes of hepatotoxic and cholestatic models of liver fibrosis

1. Marketa Jirouskova
2. Karel Harant
3. Pavel Cejnar
4. Srikant Ojha
5. Katerina Korelova
6. Lenka Sarnova
7. Eva Sticova
8. Christoph H Mayr
9. Herbert B Schiller
10. Martin Gregor

• Curated by eLife

  eLife Assessment

  This important study suggests that the composition of the extracellular matrix in a mouse model of liver fibrosis changes depending on the cause of liver fibrosis. The data could be used as a foundation for future antifibrotic therapies. The strength of evidence is convincing with respect to the use of animal models and proteomic analysis. The study provides a helpful inventory of proteins up or down-regulated.

Reviewed by eLife

Factor XI localization in human deep venous thrombus and function of activated factor XI on venous thrombus formation and hemostasis

1. Nobuyuki Oguri
2. Toshihiro Gi
3. Eriko Nakamura
4. Kazunari Maekawa
5. Eiji Furukoji
6. Hoshimi Okawa
7. Sho Kouyama
8. Saki Horiuchi
9. Akira Sawaguchi
10. Tatefumi Sakae
11. Minako Azuma
12. Yujiro Asada
13. Atsushi Yamashita

Reviewed by preLights

Kynurenine monooxygenase blockade reduces endometriosis-like lesions, improves visceral hyperalgesia, and rescues mice from a negative behavioural phenotype in experimental endometriosis

1. Ben Higgins
2. Ioannis Simitsidellis
3. Xiaozhong Zheng
4. Frances Collins
5. Natalie ZM Homer
6. Scott G Denham
7. Joanna P Simpson
8. Mike Millar
9. Lyndsey Boswell
10. Hee Y Lee
11. Yeon G Kim
12. Kyung H Park
13. Larry C Park
14. Patrick J Sweeney
15. Gerard Feraille
16. Alessandro Taddei
17. David Chagras
18. Thierry Alvarez
19. Scott P Webster
20. Andrew Horne
21. Philippa TK Saunders
22. Damian J Mole

• Curated by eLife

  eLife Assessment

  This useful study holds importance within the focused scope of endometriosis treatment, providing initial evidence of a potential new therapeutic target. The strength of the evidence is solid, as the methods, data, and analyses support the authors' conclusions regarding the specific aims. The study provides promising preliminary evidence of KMO implication in endometriosis, but it falls short of establishing a strong rationale for proposing KNS898 as a treatment for endometriosis given the limitations in evidence and mechanistic insights.

Reviewed by eLife

Enhancing bone regeneration and osseointegration using rhPTH(1-34) and dimeric R25CPTH(1-34) in an osteoporotic beagle model

1. Jeong-Oh Shin
2. Jong-Bin Lee
3. Sihoon Lee
4. Jin-Woo Kim

• Curated by eLife

  eLife Assessment

  Using a large animal model, this study demonstrated valuable findings that R25CPTH(1-34), based on a mutation associated with isolated familial hypoparathyroidism, generated an anabolic osteointegration effect comparable to that of native PTH1-34. The translational aspect of this human-to-animal work, aimed at animal-to-human translation for therapeutic purposes, should be highlighted. The study design is simple and straightforward, and the methods used are solid. The authors have addressed all the questions in their revision.

Reviewed by eLife

PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy

1. Teruhiko Yoshida
2. Khun Zaw Latt
3. Avi Z Rosenberg
4. Briana A Santo
5. Komuraiah Myakala
6. Yu Ishimoto
7. Yongmei Zhao
8. Shashi Shrivastav
9. Bryce A Jones
10. Xiaoping Yang
11. Xiaoxin X Wang
12. Vincent M Tutino
13. Pinaki Sarder
14. Moshe Levi
15. Koji Okamoto
16. Cheryl A Winkler
17. Jeffrey B Kopp

• Curated by eLife

  eLife assessment

  This study presents valuable new insights into a HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, and delineates the kidney cell types that express HIV genes and are injured in these HIV-transgenic mice. A series of compelling experiments demonstrated that PKR inhibition can ameliorate HIVAN with reversal of mitochondrial dysfunction (mainly confined to endothelial cells), a prominent feature shared in other kidney diseases. The data support that inhibition of PKR and mitochondrial dysfunction has potential clinical significance for HIVAN.

Reviewed by eLife

Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy

1. Yohei Nitta
2. Jiro Osaka
3. Ryuto Maki
4. Satoko Hakeda-Suzuki
5. Emiko Suzuki
6. Satoshi Ueki
7. Takashi Suzuki
8. Atsushi Sugie

• Curated by eLife

  eLife assessment

  This study provides valuable insights into the complex genetics of dominant optic atrophy. Leveraging a fly model, the investigators provide solid evidence, albeit with small effect sizes, for a dominant negative mechanism of certain pathogenic variants that tend to cause more severe phenotypes, a long held hypothesis in the field. The work is of high interest to those in the optic atrophy and degeneration fields.

Reviewed by eLife

Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis

1. Paul Horn
2. Jenny Norlin
3. Kasper Almholt
4. Birgitte M Viuff
5. Elisabeth D Galsgaard
6. Andreas Hald
7. Franziska Zosel
8. Helle Demuth
9. Svend Poulsen
10. Peder L Norby
11. Morten G Rasch
12. Mogens Vyberg
13. Jan Fleckner
14. Mikkel Parsberg Werge
15. Lise Lotte Gluud
16. Marco R Rink
17. Emma Shepherd
18. Ellie Northall
19. Patricia F Lalor
20. Chris J Weston
21. Morten Fog-Tonnesen
22. Philip N Newsome

• Curated by eLife

  eLife assessment

  This important paper shows that the anti-gremlin-1 (GREM1) antibody is not effective at treating liver inflammation or fibrosis. Critically, the evidence also challenges existing data on the detection of GREM1 by ELISA in serum or plasma by demonstrating that high-affinity binding of GREM1 to heparin would lead to localisation of GREM1 in the ECM or at the plasma membrane of cells. The conclusions are supported by a convincing, well-controlled set of experiments.

Reviewed by eLife

Cbfβ regulates Wnt/β-catenin, Hippo/Yap, and Tgfβ signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis

1. Wei Chen
2. Yun Lu
3. Yan Zhang
4. Jinjin Wu
5. Abigail McVicar
6. Yilin Chen
7. Siyu Zhu
8. Guochun Zhu
9. You Lu
10. Jiayang Zhang
11. Matthew McConnell
12. Yi-Ping Li

• Curated by eLife

  eLife assessment

  This fundamental work advances our understanding of the role of Cbfβ in maintaining articular cartilage homeostasis and the underlying mechanisms. The evidence supporting the conclusion is mostly convincing, although including additional experiments and discussions would have strengthened the study. This paper is of potential interest to skeletal biologists and orthopaedic surgeons who study the pathogenesis and the therapeutics of osteoarthritis.

Reviewed by eLife

Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury

1. Venkateshwari Varadharajan
2. Iyappan Ramachandiran
3. William J Massey
4. Raghav Jain
5. Rakhee Banerjee
6. Anthony J Horak
7. Megan R McMullen
8. Emily Huang
9. Annette Bellar
10. Shuhui W Lorkowski
11. Kailash Gulshan
12. Robert N Helsley
13. Isabella James
14. Vai Pathak
15. Jaividhya Dasarathy
16. Nicole Welch
17. Srinivasan Dasarathy
18. David Streem
19. Ofer Reizes
20. Daniela S Allende
21. Jonathan D Smith
22. Judith Simcox
23. Laura E Nagy
24. J Mark Brown

• Curated by eLife

  eLife assessment

  Varadharajan et al. explore the mechanistic basis of MBOAT7 SNP association with steatotic liver disease and link its function in LPI acylation to altered lipidomics of endosomal/lysosomal system and impaired TFEB mediated lysosomal biogenesis. The findings are important with theoretical and practical implications in MAFLD, alcohol-induced hepatic steatosis, and lysosomal diseases. The strength of evidence is convincing using methodology in line with current state-of-the-art.

Reviewed by eLife

Open-top Bessel beam two-photon light sheet microscopy for three-dimensional pathology

1. Won Yeong Park
2. Jieun Yun
3. Jinho Shin
4. Byung Ho Oh
5. Gilsuk Yoon
6. Seung-Mo Hong
7. Ki Hean Kim

• Curated by eLife

  eLife assessment

  This important work by Park et al. demonstrates an open-top two-photon light sheet microscopy (OT-TP-LSM) for lesser invasive evaluation of intraoperative 3D pathology. The authors provide convincing evidence for the effectiveness of this technique investigating various human cancer cells. This article will be of broad interest to biologists and, specifically, pathologists utilizing 3D optical microscopy.

Reviewed by eLife