Pathology

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. Jinwoo Kim

• Curated by eLife

  eLife assessment

  This work by Shin et al. demonstrated that a different form of PTH (R25C PTH) generated a comparable anabolic signal to rhPTH 1-34 using a large animal model. This valuable finding may have therapeutic potential in promoting bone formation or the healing process, and the methods seem solid, although there remains a concern regarding the small sample size and surgical procedure.

Reviewed by eLife

MicroRNA-26b protects against MASH development and can be efficiently targeted with lipid nanoparticles

1. Linsey JF Peters
2. Leonida Rakateli
3. Rosanna Huchzermeier
4. Andrea Bonnin-Marquez
5. Sanne L Maas
6. Cheng Lin
7. Alexander Jans
8. Yana Geng
9. Alan Gorter
10. Marion J Gijbels
11. Sander S Rensen
12. Peter Olinga
13. Tim Hendrikx
14. Marcin Krawczyk
15. Malvina Brisbois
16. Joachim Jankowski
17. Kiril Bidzhekov
18. Christian Weber
19. Erik AL Biessen
20. Ronit Shiri-Sverdlov
21. Tom Houben
22. Yvonne Döring
23. Matthias Bartneck
24. Emiel PC van der Vorst

• Curated by eLife

  eLife assessment

  This study presents valuable insights into the involvement of miR-26b in the progression of metabolic dysfunction-associated steatohepatitis (MASH). The delivery of microRNA-containing nanoparticles to reduce MASH severity has practical implications as a therapeutic strategy. Whereas convincing evidence is provided on the phenotypic changes produced by miR-26, the analyses of its precise role and function are incomplete and need more comprehensive evaluation including mechanistic studies.

Reviewed by eLife

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 Z.M. 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 T.K. Saunders
22. Damian J. Mole

• Curated by eLife

  eLife assessment

  The findings presented by the authors are useful within the focused scope of endometriosis treatment, providing a potential new therapeutic approach. The strength of the evidence is, however, incomplete, as the main claims are only partially supported by the authors' data. The research nevertheless offers promising initial evidence for KMO inhibition as a novel non-hormonal therapy for endometriosis, but further studies are needed to confirm efficacy and address any potential side effects.

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. Mikkel Parsberg Werge
14. Lise Lotte Gluud
15. Marco R Rink
16. Emma Shepherd
17. Ellie Northall
18. Patricia F Lalor
19. Chris J Weston
20. Morten Fog-Tonnesen
21. 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

Protective Role of RIPK1 Scaffolding against HDV-Induced Hepatocyte cell death and the Significance of Cytokines in Mice

1. Gracián Camps
2. Sheila Maestro
3. Laura Torella
4. Carla Usai
5. Ana Aldaz
6. Cristina Olagüe
7. Africa Vales
8. Anne Montfort
9. Bruno Ségui
10. Lester Suarez
11. Rafael Aldabe
12. Gloria Gonzalez-Aseguinolaza

Reviewed by Rapid Reviews Infectious Diseases

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