Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. N Engl J Med. 2024 Oct 24. doi: 10.1056/NEJMoa2408835. Online ahead of print.

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.

Sablik M(1), Sannier A(1), Raynaud M(1), Goutaudier V(1), Divard G(1), Astor 
BC(1), Weng P(1), Smith J(1), Garro R(1), Warady BA(1), Zahr RS(1), Twombley 
K(1), Dharnidharka VR(1), Dandamudi RS(1), Fila M(1), Huang E(1), 
Sellier-Leclerc AL(1), Tönshoff B(1), Rabant M(1), Verine J(1), Del Bello A(1), 
Berney T(1), Boyer O(1), Catar RA(1), Danger R(1), Giral M(1), Yoo D(1), 
Girardin FR(1), Alsadi A(1), Gourraud PA(1), Morelon E(1), Le Quintrec M(1), Try 
M(1), Villard J(1), Zhong W(1), Bestard O(1), Budde K(1), Chauveau B(1), Couzi 
L(1), Brouard S(1), Hogan J(1), Legendre C(1), Anglicheau D(1), Aubert O(1), 
Kamar N(1), Lefaucheur C(1), Loupy A(1).

Author information:
(1)From Université Paris Cité, INSERM Unité 970, Paris Institute for 
Transplantation and Organ Regeneration (M.S., A.S., M. Raynaud, V.G., G.D., 
D.Y., J.H., C. Legendre, O.A., C. Lefaucheur, A.L.), the Department of 
Pathology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) 
(A.S.), the Kidney Transplant Department (G.D., C. Lefaucheur) and the 
Department of Pathology (J. Verine), Saint-Louis Hospital, AP-HP, the Department 
of Pathology, Necker Hospital, AP-HP (M. Rabant), the Division of Pediatric 
Nephrology, Necker Hospital, AP-HP, Université Paris Cité (O. Boyer), the 
Department of Kidney Transplantation, Necker Hospital, AP-HP (M.T., C. Legendre, 
D.A., O.A., A.L.), and the Division of Pediatric Nephrology, Robert Debré 
Hospital, AP-HP (J.H.), Paris, the Departments of Pediatric Nephrology (M.F.) 
and Nephrology (M.L.Q.), Centre Hospitalier Universitaire (CHU) Montpellier, 
Montpellier, the Pediatric Nephrology Department, Hôpital Universitaire 
Mère-Enfant, Hospices Civils de Lyon (HCL) (A.-L.S.-L.), and the Department of 
Transplantation, Edouard Herriot University Hospital, HCL, University of Lyon I 
(E.M.), Lyon, the Department of Nephrology-Dialysis-Transplantation, CHU de 
Toulouse, Toulouse (A.B., N.K.), Nantes Université, CHU Nantes, INSERM, Center 
for Research in Transplantation and Translational Immunology, Unité Mixte de 
Recherche 1064, Institute of Urology-Nephrology Transplantation of the 
University Hospital of Nantes, Nantes (R.D., M.G., P.-A.G., S.B.), and the 
Departments of Pathology (B.C.) and Nephrology, Transplantation, Dialysis, and 
Apheresis (L.C.), CHU Bordeaux, Bordeaux - all in France; the Division of 
Nephrology, Department of Medicine, University of Wisconsin School of Medicine 
and Public Health (B.C.A.), and the Department of Pathology, University of 
Wisconsin (A.A., W.Z.) - both in Madison; Pediatric Nephrology, David Geffen 
School of Medicine at UCLA, UCLA Mattel Children's Hospital (P.W.), and 
Cedars-Sinai Comprehensive Transplant Center (E.H.) - both in Los Angeles; the 
Department of Pediatrics, University of Washington School of Medicine, Seattle 
Children's Hospital, Seattle (J.S.); the Division of Pediatric Nephrology, Emory 
University School of Medicine, Children's Pediatric Institute, Atlanta (R.G.); 
the Division of Pediatric Nephrology, University of Kansas City, Children's 
Mercy Hospital, Kansas City, MO (B.A.W.); the Division of Pediatric Nephrology 
and Hypertension, University of Tennessee Health Science Center, Le Bonheur 
Children's Hospital, Memphis (R.S.Z.); the Acute Dialysis Units, Pediatric 
Kidney Transplant, Medical University of South Carolina, Charleston (K.T.); the 
Division of Pediatric Nephrology, Hypertension, and Apheresis, Washington 
University School of Medicine and St. Louis Children's Hospital, St. Louis 
(V.R.D., R.S.D.); the Department of Pediatrics, Robert Wood Johnson Medical 
School at Rutgers University, New Brunswick, NJ (V.R.D.); the Department of 
Pediatrics I, University Children Hospital Heidelberg, Heidelberg (B.T.), and 
the Department of Nephrology and Critical Care Medicine, 
Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Berlin Institute 
of Health, Berlin (R.A.C., K.B.) - both in Germany; the Division of Abdominal 
and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva 
University Hospitals (T.B.), and the Division of Transplantation Immunology, 
University Hospital of Geneva (J. Villard), Geneva, and the Division of Clinical 
Pharmacology, Department of Medicine, and the Department of Laboratory Medicine 
and Pathology, Lausanne University Hospital, Faculty of Medicine, University of 
Lausanne, Lausanne (F.R.G.) - all in Switzerland; and the Department of 
Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital, 
Barcelona (O. Bestard).

BACKGROUND: The heterogeneous clinical presentation of graft microvascular 
inflammation poses a major challenge to successful kidney transplantation. The 
effect of microvascular inflammation on allograft outcomes is unclear.
METHODS: We conducted a cohort study that included kidney-transplant recipients 
from more than 30 transplantation centers in Europe and North America who had 
undergone allograft biopsy between 2004 and 2023. We integrated clinical and 
pathological data to classify biopsy specimens according to the 2022 Banff 
Classification of Renal Allograft Pathology, which includes two new diagnostic 
categories: probable antibody-mediated rejection and microvascular inflammation 
without evidence of an antibody-mediated response. We then assessed the 
association between the newly recognized microvascular inflammation phenotypes 
and allograft survival and disease progression.
RESULTS: A total of 16,293 kidney-transplant biopsy specimens from 6798 patients 
were assessed. We identified the newly recognized microvascular inflammation 
phenotypes in 788 specimens, of which 641 were previously categorized as 
specimens with no evidence of rejection. As compared with patients without 
rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval 
[CI], 1.5 to 3.1) among patients with microvascular inflammation without 
evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among 
patients with antibody-mediated rejection. Patients with a diagnosis of probable 
antibody-mediated rejection had a higher risk of graft failure beyond year 5 
after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 
3.5). Patients with a diagnosis of either newly recognized microvascular 
inflammation phenotype had a higher risk of progression of transplant 
glomerulopathy during follow-up than patients without microvascular 
inflammation.
CONCLUSIONS: Microvascular inflammation in kidney allografts includes distinct 
phenotypes, with various disease progression and allograft outcomes. Our 
findings support the clinical use of additional rejection phenotypes to 
standardize diagnostics for kidney allografts. (Funded by OrganX. 
ClinicalTrials.gov number, NCT06496269.).

Copyright © 2024 Massachusetts Medical Society.

DOI: 10.1056/NEJMoa2408835
PMID: 39450752


2. Fr J Urol. 2024 Sep 19;34(13):102751. doi: 10.1016/j.fjurol.2024.102751.
Online  ahead of print.

Clinical and pathological features of renal tumours among women previously 
treated for breast carcinomas - the CanSeRe study.

Peyrottes A(1), Masson-Lecomte A(2), Mongiat-Artus P(2), Nourieh M(3), Sirab 
N(3), Reyal F(4), Laas E(4), Verine J(5), Desgrandchamps F(2), Salomon A(3), 
Allory Y(3), Meria P(2).

Author information:
(1)Department of Urology and Renal transplantation, Université de Paris, AP-HP, 
Saint-Louis Hospital, 75015 Paris, France. Electronic address: 
arthur.peyrottes@aphp.fr.
(2)Department of Urology and Renal transplantation, Université de Paris, AP-HP, 
Saint-Louis Hospital, 75015 Paris, France.
(3)Department of Diagnostic and Theranostic Medicine, Versailles Saint-Quentin 
University (UVSQ), Institut Curie, Saint-Cloud, France.
(4)Department of Breast and Gynecological Surgery, Institut Curie, Paris, 
France.
(5)Department of Pathology, Université de Paris, AP-HP, Saint-Louis Hospital, 
Paris, France.

INTRODUCTION: Renal cell carcinoma (RCC) and breast carcinoma (BC) are frequent 
tumours, yet their co-occurrence in the same patient is a unique scenario. Few 
studies explored the characteristics of such patients without specific focus on 
pathological data. In this retrospective study, we aimed to describe the 
clinico-pathological features of RCC patients with a history of BC and compare 
them to a control cohort of RCC women free of previous BC.
METHODS: All adult women treated for BC at a high-volume cancer institution 
between 2007 and 2020 and who subsequently developed a RCC were retrospectively 
included. Their clinical and pathological characteristics were compared to an 
independent cohort of consecutive women undergoing percutaneous kidney tumour 
biopsy for localized kidney cancer in a second high-volume cancer institution.
RESULTS: A total of 113 patients were identified from 2 different institutions. 
We observed a lower rate of clear cell RCC in the Kidney-breast (KB) group 
compared to the Kidney-only (KO) group, suggesting a potential association 
between breast cancer and non-ccRCC. The KB group had a higher proportion of 
locally advanced tumours and high-grade lesions. Although recurrence-free 
survival favored the KO cohort, no significant difference was found in 
cancer-specific survival and overall survival rates between the groups. 
Noteworthy, patients in the KB group had a higher prevalence of family history 
of cancer.
CONCLUSION: Our findings highlight the need for further research to elucidate 
the underlying mechanisms and clinical implications of RCC coexisting with 
breast carcinoma. Understanding the characteristics of this unique population 
can guide clinical strategies and improve patient outcomes.

Copyright © 2024 Elsevier Masson SAS. All rights reserved.

DOI: 10.1016/j.fjurol.2024.102751
PMID: 39305999


3. J Chem Inf Model. 2024 Sep 9;64(17):6838-6849. doi: 10.1021/acs.jcim.4c01100. 
Epub 2024 Aug 26.

Synergistic Antimicrobial Mechanism of the Ultrashort Antimicrobial Peptide 
R(3)W(4)V with a Tadpole-like Conformation.

Cao Z(1), Shi Z(1), Tong M(2), Yang D(2), Liu L(1).

Author information:
(1)Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, 
Dezhou University, Dezhou 253023, China.
(2)Shandong Engineering Research Center of Novel Pharmaceutical Excipients, 
Sustained and Controlled Release Preparations, College of Medicine and Nursing, 
Dezhou University, Dezhou 253023, China.

Antimicrobial peptides (AMPs) are promising candidates in combating 
multidrug-resistant microorganisms because of their unique mode of action. Among 
these peptides, ultrashort AMPs (USAMPs) possess sequences containing less than 
10 amino acids and have some advantages over traditional AMPs. However, one of 
the main limitations of designing novel and highly active USAMPs is that their 
mechanism of action at the molecular level is not well-known. In this article, 
we report the antimicrobial mechanism of the USAMP verine (R3W4V) with high 
antibacterial activity against Escherichia coli. Here, by using well-tempered 
bias-exchange metadynamics simulations and long-time conventional molecular 
dynamics simulations, we evaluated whether verine exhibits the same 
antimicrobial mode of action as that of traditional AMPs. The single 
verine-membrane system exhibited a relatively flat surface with multiple shallow 
minima separated by very small energy barriers and adopted highly dynamic 
structural ensembles. Although the verine sequence is very short, it can still 
exist briefly in the center of the cell membrane in a transmembrane state. As 
the concentration of verine increased, the transmembrane conformation was 
relatively stabilized in the membrane center or proceeded toward the membrane 
bottom. The lipid bilayer membrane showed relatively large deformation, 
including the phospholipid head groups embedded inside the lipid hydrophobic 
center, accompanied by a flip-flop of some lipids. Simulation results indicated 
that verine has a specific mechanism of action different from that of 
traditional AMPs. Based on this antimicrobial mechanism of verine, we can design 
new high-potential USAMPs by enhancing the structural stability of the 
transmembrane state.

DOI: 10.1021/acs.jcim.4c01100
PMID: 39186796 [Indexed for MEDLINE]


4. Prog Urol. 2023 Dec;33(15-16):983-992. doi: 10.1016/j.purol.2023.09.033. Epub 
2023 Oct 21.

[Profile and immune environment of upper tract urothelial carcinoma].

[Article in French]

Gallon J(1), LeMaoult J(2), Verine J(3), Dumont C(4), Djouadou M(5), Carosella 
E(2), Rouass-Freiss N(2), Desgrandchamps F(5), Masson-Lecomte A(5).

Author information:
(1)Service de recherche en hémato-immunologie, Inserm U976 HIPI, université de 
Paris, CEA, Paris, France; Service d'urologie, AP-HP, hôpital Saint-Louis, 1, 
avenue Claude Vellefaux, 75010 Paris, France. Electronic address: 
jeremie.gallon@aphp.fr.
(2)Service de recherche en hémato-immunologie, Inserm U976 HIPI, université de 
Paris, CEA, Paris, France.
(3)Service d'anatomie et cytologie pathologique, AP-HP, hôpital Saint-Louis, 
Paris, France.
(4)Service d'oncologie, AP-HP, hôpital Saint-Louis, Paris, France.
(5)Service de recherche en hémato-immunologie, Inserm U976 HIPI, université de 
Paris, CEA, Paris, France; Service d'urologie, AP-HP, hôpital Saint-Louis, 1, 
avenue Claude Vellefaux, 75010 Paris, France.

INTRODUCTION AND OBJECTIVES: Upper Tract Urothelial Carcinoma (UTUC) are tumors 
that share similarities with bladder tumors. Immunotherapy is already used for 
bladder locations and appears to have interest for UTUC. In order to rationalize 
the immunotherapy development pipeline it seemed necessary to describe the 
immune infiltrate of a cohort of UTUC treated with nephroureterectomy and to 
determine the expression of a panel of immune checkpoints and co-stimulatory 
molecules on tumor cells as well as on infiltrating and circulating lymphocytes.
MATERIALS AND METHODS: This is a monocentric, prospective and exploratory work. 
Patients treated with total nephroureterectomy or segmental ureterectomy for 
presumably infiltrative (≥ T1) UTUC managed at the Saint-Louis Hospital were 
included from January 2019 to July 2020. A set of markers and immune checkpoints 
were studied by flow fluorocytometry on circulating lymphocytes (PBMCs) and 
tumor-infiltrating lymphocytes (TILs). Some markers were also studied by 
immunohistochemistry on tumor sample.
RESULTS: In total, 14 patients were included and 13 patients could be analyzed. 
1 patient had no residual tumor. 5 tumors out of the 12 (41.7%) showed a 
lymphocytic inflammatory infiltrate. PD1 was the most represented checkpoint 
with a median expression rate of 41.4% on CD4+ TILs and 3.89% on circulating 
CD4+ T cells. This rate was 62.4% and 7.45% respectively on CD8+ T cells. TIGIT 
was the second most represented marker with a median expression rate on 
tumor-infiltrating CD4+ T cells of 25% and 2.9% on circulating CD4+ T cells. The 
median expression level of TIGIT on tumor-infiltrating CD8+ T cells was 23.3% 
and 3.2% on circulating CD8+ T cells. ICOS was highly expressed on CD4+ TILS 
with a median of 33.9% in contrast to CD8+ TILS (median: 6.67%). Variable 
expression of other checkpoints (ILT2, TIM3, LAG3 and OX40) was found without 
clear trend.
CONCLUSION: This exploratory work highlighted that PD1 was the most represented 
checkpoint. TIGIT was the second most represented checkpoint while ICOS, TIM3 
and LAG3 were 3 other checkpoints whose expression was found to be less 
important. ILT2 and OX40 appeared to be weakly expressed.
LEVEL OF EVIDENCE: II.

Copyright © 2023 Elsevier Masson SAS. All rights reserved.

DOI: 10.1016/j.purol.2023.09.033
PMID: 37872060 [Indexed for MEDLINE]


5. Mod Pathol. 2023 Nov;36(11):100300. doi: 10.1016/j.modpat.2023.100300. Epub
2023  Aug 7.

Transcriptomic Profiling of Upper Tract Urothelial Carcinoma: Bladder Cancer 
Consensus Classification Relevance, Molecular Heterogeneity, and Differential 
Immune Signatures.

Fontugne J(1), Xylinas E(2), Krucker C(3), Dixon V(3), Groeneveld CS(4), Pinar 
U(5), Califano G(6), Bucau M(7), Verine J(8), Desgrandchamps F(9), Hermieu 
JF(6), Radvanyi F(10), Allory Y(11), Masson-Lecomte A(9).

Author information:
(1)Department of Pathology, Institut Curie, Saint-Cloud, France; Institut Curie, 
CNRS, UMR144, Equipe labellisée Ligue Contre le Cancer, Paris Sciences et 
Lettres Research University, Paris, France; Université Paris-Saclay, Université 
de Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France. 
Electronic address: jacqueline.fontugne@curie.fr.
(2)Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Department of 
Urology, Bichat-Claude Bernard Hospital, Paris, France; Université de Paris, 
INSERM U976, Human Immunology, Pathophysiology, Immunotherapy, Paris, France.
(3)Department of Pathology, Institut Curie, Saint-Cloud, France; Institut Curie, 
CNRS, UMR144, Equipe labellisée Ligue Contre le Cancer, Paris Sciences et 
Lettres Research University, Paris, France.
(4)Institut Curie, CNRS, UMR144, Equipe labellisée Ligue Contre le Cancer, Paris 
Sciences et Lettres Research University, Paris, France; Ligue Nationale Contre 
le Cancer, Cartes d'Identité des Tumeurs Program, Paris, France.
(5)Assistance Publique-Hôpitaux de Paris, Department of Urology, Saint-Louis 
Hospital, Paris, France.
(6)Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Department of 
Urology, Bichat-Claude Bernard Hospital, Paris, France.
(7)Assistance Publique-Hôpitaux de Paris, Department of Pathology, Bichat-Claude 
Bernard Hospital, Paris, France.
(8)Assistance Publique-Hôpitaux de Paris, Department of Pathology, Saint-Louis 
Hospital, Paris, France.
(9)Assistance Publique-Hôpitaux de Paris, Department of Urology, Saint-Louis 
Hospital, Paris, France; Université Paris Cité, Service de Recherche en 
Hémato-Immunologie, CEA, INSERM U976, Human Immunology, Pathophysiology, 
Immunotherapy, Paris, France.
(10)Institut Curie, CNRS, UMR144, Equipe labellisée Ligue Contre le Cancer, 
Paris Sciences et Lettres Research University, Paris, France.
(11)Department of Pathology, Institut Curie, Saint-Cloud, France; Institut 
Curie, CNRS, UMR144, Equipe labellisée Ligue Contre le Cancer, Paris Sciences et 
Lettres Research University, Paris, France; Université Paris-Saclay, Université 
de Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.

Analyses of large transcriptomics data sets of muscle-invasive bladder cancer 
(MIBC) have led to a consensus classification. Molecular subtypes of upper tract 
urothelial carcinomas (UTUCs) are less known. Our objective was to determine the 
relevance of the consensus classification in UTUCs by characterizing a novel 
cohort of surgically treated ≥pT1 tumors. Using immunohistochemistry (IHC), 
subtype markers GATA3-CK5/6-TUBB2B in multiplex, CK20, p16, Ki67, mismatch 
repair system proteins, and PD-L1 were evaluated. Heterogeneity was assessed 
morphologically and/or with subtype IHC. FGFR3 mutations were identified by 
pyrosequencing. We performed 3'RNA sequencing of each tumor, with multisampling 
in heterogeneous cases. Consensus classes, unsupervised groups, and 
microenvironment cell abundance were determined using gene expression. Most of 
the 66 patients were men (77.3%), with pT1 (n = 23, 34.8%) or pT2-4 stage UTUC 
(n = 43, 65.2%). FGFR3 mutations and mismatch repair-deficient status were 
identified in 40% and 4.7% of cases, respectively. Consensus subtypes robustly 
classified UTUCs and reflected intrinsic subgroups. All pT1 tumors were 
classified as luminal papillary (LumP). Combining our consensus classification 
results with those of previously published UTUC cohorts, LumP tumors represented 
57.2% of ≥pT2 UTUCs, which was significantly higher than MIBCs. Ten patients 
(15.2%) harbored areas of distinct subtypes. Consensus classes were associated 
with FGFR3 mutations, stage, morphology, and IHC. The majority of LumP tumors 
were characterized by low immune infiltration and PD-L1 expression, in 
particular, if FGFR3 mutated. Our study shows that MIBC consensus classification 
robustly classified UTUCs and highlighted intratumoral molecular heterogeneity. 
The proportion of LumP was significantly higher in UTUCs than in MIBCs. Most 
LumP tumors showed low immune infiltration and PD-L1 expression and high 
proportion of FGFR3 mutations. These findings suggest differential response to 
novel therapies between patients with UTUC and those with MIBC.

Copyright © 2023 United States & Canadian Academy of Pathology. Published by 
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.modpat.2023.100300
PMID: 37558130 [Indexed for MEDLINE]