Pharmacology and Toxicology

  1. A mechanism of uncompetitive inhibition of the serotonin transporter

    1. Shreyas Bhat
    2. Ali El-Kasaby
    3. Ameya Kasture
    4. Danila Boytsov
    5. Julian B Reichelt
    6. Thomas Hummel
    7. Sonja Sucic
    8. Christian Pifl
    9. Michael Freissmuth
    10. Walter Sandtner

    • Curated by eLife

      eLife assessment

      This study presents the important finding of an unusual uncompetitive inhibitor (ECSI#6) of the serotonin transporter that removes the neurotransmitter serotonin from the synaptic cleft. Through careful and comprehensive analysis, the authors convincingly show that the molecule most likely binds to the inward-facing and K+-bound state and that it assists in folding and targeting the transporter. The work will be of interest to those engaged in biophysical analyses of the serotonin transporter, and colleagues developing pharmacological chaperoning strategies for transporters in general.

    Reviewed by eLife

    5 evaluationsAppears in 1 listLatest version Latest activity

  2. Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals

    1. Lijuan Xu
    2. Xinyao Zhang
    3. Yin Zhao
    4. Xiaorui Gang
    5. Tao Zhou
    6. Jialing Han
    7. Yang Cao
    8. Binyan Qi
    9. Shuning Song
    10. Xiaojie Wang
    11. Yuanbo Liang

    • Curated by eLife

      eLife assessment

      This manuscript proposes that metformin protects against elevated intraocular pressure and oxidative injury by regulating cytoskeleton remodeling through the integrin/ROCK pathway, thus providing a new direction for further exploration toward the treatment of primary open-angle glaucoma as well as investigation of oxidative injury in multiple settings.

    Reviewed by eLife

    3 evaluationsAppears in 1 listLatest version Latest activity

    1. Guang Wang
    2. Yong-Feng Wang
    3. Jiang-Lan Li
    4. Ru-Ji Peng
    5. Xin-Yin Liang
    6. Xue-Dong Chen
    7. Gui-Hua Jiang
    8. Jin-Fang Shi
    9. Yang-Hu Si-Ma
    10. Shi-Qing Xu
    11. 苏州大学苏州医学院基础医学与生物科学学院, 江苏 苏州215123, 中国
    12. 苏州大学第一附属医院临床检验科, 江苏 苏州215006, 中国
    13. School of Biology and Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, China
    14. Department of Clinical Laboratory, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China

    • Curated by eLife

      Evaluation Summary:

      The authors present a manuscript addressing an important unmet need, specifically focused on understanding the effects of high protein on hematopoiesis. This information can be of interest to basic biologists and clinicians who specialize in the areas of various diseases associated with elevated protein concentration (e.g. infections, inflammation, multiple myeloma, renal failure, etc). This is in part what makes for the complexity in studying this entity as the consequences of such disparate diseases are difficult to parcel out as causes of which specific disease manifestations. Furthermore, the presented work is done in an invertebrate model without additional confirmation in other model systems. Taken together, the work, which is plentiful in experiments, provides an incomplete understanding of cause and effect, leading to overinterpretation of results and overstating of derived conclusions.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Reviewed by eLife

    3 evaluationsAppears in 1 listLatest version Latest activity

  4. Robust and Efficient Assessment of Potency (REAP) as a quantitative tool for dose-response curve estimation

    1. Shouhao Zhou
    2. Xinyi Liu
    3. Xinying Fang
    4. Vernon M Chinchilli
    5. Michael Wang
    6. Hong-Gang Wang
    7. Nikolay V Dokholyan
    8. Chan Shen
    9. J Jack Lee

    • Curated by eLife

      Evaluation Summary:

      This article proposes methodology and accompanying software for robustly fitting dose-response curves where response is a number between 0 and 1. When response is transformed using the common logistic transformation, values close to 0 or 1 become large in magnitude, unduly influencing the fitted curve after back-transformation and introducing bias in the estimate of certain parameters. The proposed approach, called Robust and Efficient Assessment of Potency, is less perturbed by these extreme measurements.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife

    3 evaluationsAppears in 1 listLatest version Latest activity

  5. Hemin shows antiviral activity in vitro , possibly through suppression of viral entry mediators

    1. Mehmet Altay Unal
    2. Ceylan Verda Bitirim
    3. Julia Somers
    4. Gokce Yagmur Summak
    5. Omur Besbinar
    6. Ebru Kocakaya
    7. Cansu Gurcan
    8. Hasan Nazir
    9. Zeynep Busra Aksoy Ozer
    10. Sibel Aysil Ozkan
    11. Sidar Bereketoglu
    12. Aykut Ozkul
    13. Emek Demir
    14. Kamil Can Akcali
    15. Acelya Yilmazer

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity

  6. SARS-CoV-2 Subunit Virus-Like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study

    1. A.V. Vakhrusheva
    2. A.V. Kudriavtsev
    3. N.A. Kryuchkov
    4. R.V. Deev
    5. M.E. Frolova
    6. K.A. Blagodatskikh
    7. M. Djonovic
    8. A.A. Nedorubov
    9. E. Odintsova
    10. A.V. Ivanov
    11. E.A. Romanovskaya-Romanko
    12. M.A. Stukova
    13. A.A. Isaev
    14. I.V. Krasilnikov

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity

  7. Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types

    1. David J Jörg
    2. Doris H Fuertinger
    3. Alhaji Cherif
    4. David A Bushinsky
    5. Ariella Mermelstein
    6. Jochen G Raimann
    7. Peter Kotanko

    • Curated by eLife

      Evaluation Summary:

      This paper will be of interest to the pharmacology community with interest in available drug treatments for osteoporosis and how to optimize these. The key findings of the paper are based on in silico results and indicate that combined drug treatments may be more efficient in treatment of osteoporosis. This could have a significant impact on clinical management of osteoporosis patients.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife

    3 evaluationsAppears in 1 listLatest version Latest activity

  8. FSH-blocking therapeutic for osteoporosis

    1. Sakshi Gera
    2. Tan-Chun Kuo
    3. Anisa Azatovna Gumerova
    4. Funda Korkmaz
    5. Damini Sant
    6. Victoria DeMambro
    7. Karthyayani Sudha
    8. Ashley Padilla
    9. Geoffrey Prevot
    10. Jazz Munitz
    11. Abraham Teunissen
    12. Mandy MT van Leent
    13. Tomas GJM Post
    14. Jessica C Fernandes
    15. Jessica Netto
    16. Farhath Sultana
    17. Eleanor Shelly
    18. Satish Rojekar
    19. Pushkar Kumar
    20. Liam Cullen
    21. Jiya Chatterjee
    22. Anusha Pallapati
    23. Sari Miyashita
    24. Hasni Kannangara
    25. Megha Bhongade
    26. Puja Sengupta
    27. Kseniia Ievleva
    28. Valeriia Muradova
    29. Rogerio Batista
    30. Cemre Robinson
    31. Anne Macdonald
    32. Susan Hutchison
    33. Mansi Saxena
    34. Marcia Meseck
    35. John Caminis
    36. Jameel Iqbal
    37. Maria I New
    38. Vitaly Ryu
    39. Se-Min Kim
    40. Jay J Cao
    41. Neeha Zaidi
    42. Zahi A Fayad
    43. Daria Lizneva
    44. Clifford J Rosen
    45. Tony Yuen
    46. Mone Zaidi

    • Curated by eLife

      Evaluation Summary:

      The authors describe a comprehensive characterization of a new humanized FSH blocking antibody (MS-Hu6), which they have studied in-depth in terms of its efficacy on bone and fat tissues. They provide compelling data on mouse and monkey species with a complete evaluation of its pharmacokinetics and biodistribution and characterize its effect for the treatment of obesity and bone loss. It is an important contribution and will be useful to a general readership in endocrinology, bone and fat metabolism.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Reviewed by eLife

    3 evaluationsAppears in 1 listLatest version Latest activity

  9. Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

    1. Flavio P. Veras
    2. Giovanni F. Gomes
    3. Bruna M. S. Silva
    4. Diego B. Caetité
    5. Cicero J. L. R. Almeida
    6. Camila Meirelles S. Silva
    7. Ayda H. Schneider
    8. Emily S. Corneo
    9. Caio S. Bonilha
    10. Sabrina S. Batah
    11. Ronaldo Martins
    12. Eurico Arruda
    13. Alexandre T. Fabro
    14. José C. Alves-Filho
    15. Thiago M. Cunha
    16. Fernando Q. Cunha

    Reviewed by Rapid Reviews Infectious Diseases, ScreenIT

    4 evaluationsAppears in 2 listsLatest version Latest activity

  10. Methylene Blue Is a Nonspecific Protein–Protein Interaction Inhibitor with Potential for Repurposing as an Antiviral for COVID-19

    1. Sung-Ting Chuang
    2. Henrietta Papp
    3. Anett Kuczmog
    4. Rebecca Eells
    5. Jose M. Condor Capcha
    6. Lina A. Shehadeh
    7. Ferenc Jakab
    8. Peter Buchwald

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity
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