Endometriosis, a chronic inflammatory condition affecting an estimated one in ten women of reproductive age, has long frustrated clinicians with its stubborn tendency to recur despite surgery and hormone therapy. A new review published in Reproductive Sciences argues that the answer to this therapeutic failure may lie in a single transcription factor: ZEB1, or Zinc Finger E-Box Binding Homeobox 1. Written by Gaurav Doshi and Sanket Shirodkar of SVKM’s Dr. Bhanuben Nanavati College of Pharmacy in Mumbai, the review synthesises evidence from across the field to position ZEB1 as a master molecular integrator—converging hormonal, inflammatory and epigenetic signals into a single programme that drives lesion establishment, invasiveness and drug resistance.

The biological centrepiece of the review is epithelial–mesenchymal transition, or EMT, the process by which epithelial cells lose their adhesive, stationary character and acquire the migratory, invasive traits of mesenchymal cells. In endometriosis, EMT is thought to be essential for the survival of endometrial cells that reflux into the pelvic cavity during menstruation and subsequently implant on peritoneal surfaces, ovaries and other ectopic sites. ZEB1 sits at the apex of this programme. It suppresses CDH1, the gene encoding E-cadherin, the principal adhesion molecule holding epithelial sheets together, and in doing so dismantles the cell–cell junctions that would otherwise keep ectopic cells anchored and vulnerable. The review details how ZEB1 accomplishes this repression by recruiting chromatin-remodelling machinery, notably the SWI/SNF ATPase subunit BRG1, to the E-cadherin promoter, effectively silencing it epigenetically. The result is a stabilised mesenchymal differentiation that permits attachment, invasion and, ultimately, the vascularisation required for a lesion to persist.

Crucially, the authors argue that ZEB1 is not merely one EMT factor among many, such as SNAI1, SNAI2 or its paralog ZEB2, but a systems-level hub. Immunohistochemical and molecular studies have repeatedly shown selective upregulation of ZEB1 in ectopic endometriotic lesions compared with matched eutopic endometrium, and its expression is particularly pronounced in deep infiltrating disease. One frequently cited clinical study found ZEB1 expression to be a potential indicator of invasive endometriosis, while a pilot investigation of different disease phenotypes has extended these observations across superficial, ovarian and deep infiltrating subtypes. Measurable ZEB levels have even been detected in plasma and peritoneal fluid of patients with endometriosis and infertility, raising the prospect of ZEB-family proteins as circulating biomarkers.

Perhaps the most consequential section of the review concerns the bidirectional crosstalk between ZEB1 and sex steroid signalling. Endometriosis is a hormone-dependent disease, and its defining therapeutic problem is progesterone resistance: lesions fail to respond to the progestational drugs used to suppress them. The review marshals evidence that oestrogen, specifically 17β-estradiol, induces ZEB1 expression, and that ZEB1 in turn suppresses progesterone receptor pathways. This creates a self-reinforcing circuit in which the oestrogen-ZEB1 axis dismantles the molecular machinery that progesterone therapy depends upon. Experimental work has demonstrated that high ZEB1 expression accompanies 17β-estradiol-induced EMT in endometriotic cells, and parallel findings from other hormone-driven diseases reinforce the mechanism: in breast cancer, ZEB1 induces oestrogen receptor-α promoter hypermethylation and confers antiestrogen resistance, and ZEB-family members have been shown to regulate endocrine therapy sensitivity through both canonical and non-canonical routes. In endometriosis, EMT itself has been shown to contribute to the downregulation of progesterone receptor expression in lesions, and the near-uniform loss of progesterone receptor isoform B in ectopic tissue is a long-standing observation that the ZEB1 framework now helps to explain mechanistically.

The review also devotes substantial attention to the non-coding RNA dimension of ZEB1 regulation, describing a multilayered feedback architecture that locks the mesenchymal state in place. The miR-200 family of microRNAs normally targets the 3′ untranslated regions of ZEB1 and ZEB2 transcripts, holding EMT in check. In ectopic lesions, this double-negative feedback loop is subverted: ZEB1 represses miR-200 transcription, and the resulting loss of miR-200 pressure allows ZEB1 protein to accumulate. Long non-coding RNAs add another tier. The lncRNA AFAP1-AS1, for example, promotes EMT in endometriosis in a ZEB1-correlated manner, and the metastasis-associated transcript MALAT1 has been implicated in the same circuitry, with miR-200c suppressing endometriotic progression in vitro and in vivo by targeting it. Circular RNAs complete the picture. The circRNA circZFPM2 has been shown to promote EMT by sponging miR-205-5p and thereby releasing ZEB1 from repression, while hsa_circ_0063526 acts through the miR-141-5p/EMT axis and circATRNL1 acts upstream by upregulating the EMT cofactor YAP1. Together these competing endogenous RNA networks—a concept also validated in metastatic cancer by J Clin Invest work—build a ceRNA web that perpetuates ZEB1 expression long after the initial pro-EMT stimulus has passed.

The authors then connect ZEB1 to the two great downstream consequences of endometriotic lesions: chronic inflammation and fibrosis. Through interactions with the TGF-β pathway—upstream signals such as TGF-β1 activate SMAD2/3, which cooperate with ZEB1 to drive the mesenchymal programme—ZEB1-linked cells reshape the lesion microenvironment. Fibroblast-to-myofibroblast transdifferentiation, marked by α-smooth muscle actin expression, generates the dense extracellular matrix characteristic of endometriotic implants, and analogous MRTF-A–ZEB1–IRF9 axes have been documented in renal fibrosis. Inflammation completes the loop: pro-inflammatory cytokines such as TNF-α, IL-6 and IL-10, and peritoneal fluid cytokine profiles that differ across endometriosis subphenotypes, feed back into EMT signalling through MAPK, ERK, PI3K/AKT and NF-κB pathways, while immune evasion mechanisms—including indoleamine 2,3-dioxygenase-mediated suppression of natural killer cell cytotoxicity—shield ectopic tissue from immune clearance. ZEB1’s own roles in immune cell biology and in macrophage efferocytosis and mitochondrial dynamics add further dimensions to this immunological interplay.

A distinctive strength of the review is its engagement with modern genomics and the heterogeneity it has revealed. Single-cell transcriptomic analyses of endometriosis, published in Nature Genetics and the Journal of Pathology, have identified distinct hormonal, immunologic and inflammatory signatures among the cell populations constituting lesions, and spatial transcriptomics is beginning to map how intermediate fibroblast and myeloid cell distributions shape lesion architecture. ZEB1 expression, the authors note, is not uniform: it varies by lesion subtype, anatomical site and microenvironmental context, which helps explain why superficial peritoneal, ovarian endometrioma and deep infiltrating disease behave so differently and respond so unevenly to therapy. This heterogeneity argues strongly against a one-size-fits-all anti-ZEB1 strategy and supports the emerging precision-medicine framing of the oestrogen-ZEB1-TGF-β axis as the central therapeutic target.

The review is refreshingly candid about the translational paradox at the heart of any ZEB1-directed therapy. Far from being a purely pathological molecule, ZEB1 has indispensable physiological functions in the female reproductive tract. In vitro studies show that ZEB1 modulates endometrial receptivity through EMT in endometrial epithelial cells, and work in mice demonstrates that it promotes EMT of endometrial epithelium and plays a critical role in embryo implantation. ZEB1 is also detected in granulosa cells of women undergoing IVF, regulates wound angiogenesis and closure, participates in corneal homeostasis, and contributes to endometrial repair during menstruation through epithelial migration and mesenchymal–epithelial transition. Blanking ZEB1 systemically, therefore, risks impairing fertility, tissue regeneration and wound healing—the very outcomes clinicians are trying to protect. Any therapeutic strategy would need to be lesion-specific, temporally controlled and carefully titrated, perhaps by targeting upstream oestrogen-driven induction, the TGF-β/ALK5 arm, the non-coding RNA sponges, or post-translational stabilisation mechanisms such as ZEB1 acetylation, phosphorylation and ubiquitin-proteasome turnover via regulators like USP51 and SIAH1/2.

The authors also stress the need for better experimental models to establish causal rather than merely correlative relevance. shRNA- and siRNA-based knockdown of ZEB1 in endometriotic cells, three-dimensional patient-derived endometriosis models for drug evaluation, and multi-omics approaches that integrate transcriptomic, epigenomic and proteomic data—including recent ubiquitination-focused studies of endometriosis fibrosis—are all highlighted as tools that could convert the ZEB1 hypothesis into testable interventions. Biomarker development is another avenue: ZEB-family levels in plasma and peritoneal fluid, in combination with existing miRNA signatures, could one day support non-invasive diagnosis, a long-standing unmet need given that current detection still relies on laparoscopy.

Ultimately, the review’s central claim is that the oestrogen–ZEB1–TGF-β axis functions as a signalling hub through which the hormonal, inflammatory and epigenetic drivers of endometriosis converge and perpetuate one another. By identifying ZEB1 as the point of integration, the authors provide a mechanistic scaffold that could explain progesterone resistance, fibrotic progression and recurrence within a single framework, and they chart a cautious but concrete path toward mechanism-based, lesion-specific precision therapies. For a disease that has historically been managed with blunt hormonal and surgical instruments, the prospect of intervening at the level of a single, druggable transcriptional circuit represents one of the more compelling conceptual advances in endometriosis research in recent years.

The Marcus Foundation has awarded $28.7 million to Chuck Murry, MD, PhD, director of the USC Stem Cell Center, to support a clinical trial testing a stem cell-based therapy intended to regenerate heart muscle damaged by a severe heart attack. The award, the largest the foundation has given to the University of Southern California and one of its largest contributions to academic medicine, will fund both the planned human study and a parallel research program examining how the immune system responds to transplanted cardiac cells.

The trial is scheduled to begin in 2027 at Keck Hospital of USC in partnership with the USC Cardiac and Vascular Institute. A second clinical site will be established at the University of Washington, where elements of the technology were originally developed. The first phase will enroll approximately 18 patients who have experienced extensive myocardial infarction, the medical term for a heart attack that destroys part of the heart’s muscular wall.

Patients in the study will receive stem-cell-derived heart muscle cells delivered into regions damaged by the infarction. The primary goals will be to evaluate safety and determine whether the procedure is feasible in people with severe cardiac injury. Investigators will also monitor early biological signals, including whether the transplanted cells remain active, integrate with the injured tissue and produce measurable changes in cardiac performance during recovery and long-term follow-up.

A heart attack occurs when blood flow through a coronary artery is blocked, depriving cardiac muscle of oxygen. Within minutes, cells in the affected region begin to die, and the resulting scar tissue lacks the contractile properties of healthy myocardium. Unlike tissues such as skin or blood, adult human heart muscle has only a limited capacity for self-repair. As a result, a large infarction can weaken the heart’s pumping function, increase the risk of heart failure and leave survivors unable to perform ordinary activities without fatigue or breathlessness.

Current cardiovascular treatments can reopen blocked arteries, limit further injury and help the remaining heart muscle work more efficiently. They cannot, however, routinely replace the cardiomyocytes that have already been lost. Murry’s research program is aimed at addressing that biological gap by producing replacement heart muscle cells in the laboratory and delivering them directly to damaged tissue. The strategy represents a shift from supporting a failing heart to attempting to rebuild part of its contractile apparatus.

The transplanted cells are being developed as a form of cellular therapy, in which living cells act as the therapeutic agent rather than serving merely as a vehicle for a drug. According to Murry, the cells are intended to become active within the injured heart, contribute to repair and synchronize with surrounding muscle. Achieving that outcome requires more than placing new cells into scarred tissue: the cells must survive, connect functionally with the host myocardium and avoid creating dangerous electrical disturbances or abnormal rhythms. The initial trial is therefore designed principally to establish safety before testing therapeutic effectiveness in larger patient groups.

The foundation’s funding will also support research into the immune response triggered by cell transplantation. Even cells created from stem cells can be recognized as foreign by the recipient’s immune system, potentially leading to inflammation or destruction of the transplanted population. Patients who receive cellular grafts may consequently require immunosuppressive drugs, which can increase susceptibility to infection and produce other long-term complications. Researchers will study how immune cells interact with the implanted cardiac cells and investigate methods that could reduce or eventually eliminate the need for chronic immunosuppression.

The work builds on approximately three decades of research by Murry and his collaborators to move regenerative cardiology from laboratory experiments toward clinical treatment. The program includes gene-edited cellular technology, intended to improve the compatibility or performance of therapeutic cells in the human body. The precise effectiveness of the approach will not be known until it is tested in patients, and the small 2027 cohort will not be large enough to determine whether the therapy improves survival or prevents heart failure. Those questions would require subsequent trials involving substantially more participants and longer observation.

The Marcus Foundation described the project as a potential turning point for regenerative medicine, while USC leaders said the investment could create a platform for developing additional cellular therapies. The immediate scientific challenge is to determine whether transplanted heart muscle cells can be delivered safely and function meaningfully within severely damaged human hearts. If the trial meets its safety and feasibility objectives, it could provide the clinical evidence needed to advance a new generation of treatments for myocardial infarction—therapies designed not only to help patients live with damaged cardiac tissue, but to restore some of the function that conventional medicine cannot yet replace.

Subject of Research: Stem cell-based regenerative therapy for heart muscle damaged by myocardial infarction

Article Title: $28.7 Million Award Supports USC Trial of Stem Cell Therapy to Regenerate Heart Muscle After Heart Attack

Web References: The Marcus Foundation: https://marcusfoundation.org/; USC Stem Cell Center: https://stemcell.keck.usc.edu/; Chuck Murry Lab: https://murrylab.usc.edu/charles-chuck-murry-md-phd/; USC Cardiac and Vascular Institute: https://www.keckmedicine.org/services/cardiovascular/; Keck School of Medicine of USC: https://keck.usc.edu/

Image Credits: Steve Cohn

Keywords: Heart disease, myocardial infarction, heart attack, heart muscle, stem cell research, stem cell therapy, cell therapy, regenerative medicine, cardiovascular disorders, heart failure, clinical trial, cardiac regeneration

A new study finds plantations respond strongly to carbon dioxide, especially while young.

A groundbreaking imaging technology developed by researchers at the University of Oklahoma promises to revolutionize liver transplant evaluations by enabling more comprehensive and rapid assessments of donor organ health. With thousands of patients awaiting liver transplants nationwide, transplant teams urgently need tools that can deliver swift, accurate insights without invasive procedures. The team, led by Dr. Qinggong Tang, has adapted polarization-sensitive optical coherence tomography (PS-OCT)—an advanced imaging modality originally utilized in retinal scans—to noninvasively evaluate donor livers at high resolution.

Traditional liver assessments rely heavily on biopsies, where small tissue samples are extracted and examined for signs of disease or damage. While considered the gold standard, biopsies are inherently limited, providing only a microscopic snapshot of a vast organ that may vary in condition. This narrow sampling can cause uncertainty, sometimes leading to the discard of viable organs. The OU team sought to overcome these limitations by employing PS-OCT, which not only captures detailed cross-sectional images of liver tissue but also measures its polarization properties, revealing subtle structural and biochemical features linked to liver health.

The engineers designed a portable PS-OCT system optimized for clinical and operating room environments, allowing transplant teams to scan liver surfaces quickly and noninvasively. The imaging data are then analyzed using advanced artificial intelligence algorithms, co-developed with Dr. Chongle Pan’s computer science lab. These AI tools quantify critical parameters indicative of hepatic steatosis (fat accumulation) and inflammation, two primary factors influencing liver viability. By training their models on datasets from over thirty clinical cases—comparing PS-OCT results with biopsy outcomes and post-transplant organ function—the researchers demonstrated strong correlations between imaging biomarkers and actual clinical metrics.

Beyond providing a more holistic view of donor liver condition, PS-OCT could enhance decision-making speed, potentially expanding the pool of organs deemed suitable for transplantation by identifying healthy tissue regions missed by biopsy. Such improvements may reduce organ discard rates and improve transplant success. Encouraged by initial findings, the OU team plans a large multisite clinical trial involving institutions like UT Southwestern and the Cleveland Clinic to validate and refine this approach across diverse patient populations.

This work exemplifies OU’s interdisciplinary innovation platform that integrates optical bioimaging, machine learning, pathology, and organ perfusion technology to translate engineering advances directly into clinical practice. The researchers also intend to extend PS-OCT evaluation methods to other organs, including kidneys and lungs, widening the impact of this technology.

Supported by National Science Foundation grants and institutional partnerships, the team’s efforts mark a significant step toward redefining how transplanted organs are assessed. Dr. Tang emphasizes that this is just the beginning, envisioning a future where noninvasive, AI-enhanced imaging facilitates safer, faster, and more effective organ transplantation worldwide.

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Subject of Research: Donor liver evaluation using advanced imaging techniques
Article Title: Human donor liver viability evaluation with polarization-sensitive optical coherence tomography
News Publication Date: 24-Jun-2026
Web References: http://dx.doi.org/10.1126/scitranslmed.adv7124
Image Credits: University of Oklahoma / Ellie Pinter

Keywords

Organ transplantation, Optical coherence tomography, Polarization-sensitive imaging, Liver viability, Artificial intelligence, Biomedical imaging, Noninvasive diagnostics, Medical innovation

Nearly half of American patients diagnosed with kidney failure face a significant hurdle that remains largely unnoticed: the daunting path from referral for kidney transplantation to actually being listed as a transplant candidate. A groundbreaking national study spearheaded by researchers from NYU Langone Health reveals that only about 19 percent of these patients complete the rigorous evaluation process required to join the kidney transplant waitlist. Alarmingly, nearly 48 percent never even commence this critical phase, underscoring a systemic challenge within transplant medicine that urgently warrants comprehensive attention.

Kidney transplantation is widely regarded as the optimal treatment for end-stage renal disease, significantly enhancing both survival rates and quality of life over long-term dialysis. Despite extensive research focusing on outcomes and management once patients are waitlisted or transplanted, the early stages—particularly the transition from referral to evaluation—have remained remarkably underexplored. The new study addresses this knowledge gap by meticulously analyzing data that track patient progression (or dropout) through each sequential step: referral, evaluation, waitlisting, and transplantation.

Leveraging the formidable Epic Cosmos database, which aggregates over 300 million electronic health records from more than 1,850 medical institutions—including over a third of all U.S. transplant centers—the research team was able to follow 720,348 adult patients referred for kidney transplantation between 2014 and 2025. By applying advanced statistical modeling, the researchers dissected how variables such as demographic factors, socioeconomic status, geographic location, and medical complexities influence patient trajectories through the transplant pipeline.

One of the study’s most compelling revelations is the multifaceted nature of barriers patients face long before they arrive on the transplant waitlist. Particularly vulnerable are unmarried individuals, those categorized with severe obesity, and patients residing in rural areas. These groups demonstrated disproportionately lower rates of starting and completing the transplant evaluation. The researchers suggest that limited social support, compounded by logistical challenges in accessing transplant centers mostly concentrated in urban settings, profoundly affects these disparities.

Language barriers and poverty add further layers of complexity. Older patients, Spanish speakers, and economically disadvantaged populations exhibited reduced odds of progressing beyond referral. The evaluation process itself, demanding repeated visits for comprehensive testing—including hematologic assays, radiologic imaging like chest X-rays, and oncologic screenings—can extend over months. This prolonged and intricate schedule poses significant strain on patients, particularly those simultaneously managing frequent dialysis treatments.

Institutional factors also shape patient outcomes. Smaller transplant centers, often with constrained resources and fewer transplant slots, tend to adopt more conservative patient selection criteria. This resource scarcity may lead to heightened risk aversion, amplifying the likelihood that individuals are filtered out early in the process. In contrast, larger centers with expansive infrastructure appear better suited to support patients through the complex evaluation stages, enhancing access equity.

Beyond healthcare infrastructure, psychosocial elements emerge as crucial determinants. The study highlights the importance of marital status and social support networks, which facilitate navigating the exhaustive appointment schedule and the psychological burden of chronic illness management. Candidates lacking robust social backings are more susceptible to discontinuing the transplant workup, emphasizing that transplant candidacy extends beyond physiological suitability to encompass holistic patient contexts.

The authors underscore that the transplant evaluation pathway remains one of the most intricate and strenuous journeys in medical care, entailing multifaceted specialist consultations, laboratory testing, and patient education. Each phase demands adequate patient understanding, resource availability, and logistical feasibility, accentuating the necessity for patient-centered strategies to democratize access.

Conor Donnelly, MD, the study’s lead author and PhD candidate at NYU Grossman School of Medicine, reflects on the striking influence of non-medical factors, stating the interplay of geography, healthcare center characteristics, and social environment decisively shapes transplant waitlisting outcomes. He advocates for system-level reforms targeting these upstream barriers to broaden equitable transplant access.

Allan B. Massie, PhD, co-senior author, emphasizes the potential impact of tailored educational efforts and patient navigation services to demystify and streamline the evaluation process. By reducing administrative burden and fostering comprehensible pathways, health systems can meaningfully increase the number of patients transitioning from referral to active waitlisting.

Similarly, Michal A. Mankowski, PhD, co-senior author and assistant professor of surgery, notes this study paves the way for probing analogous barriers in other organ transplant domains, each characterized by distinct logistical and clinical considerations. Expanding this research is vital for holistic transplant equity improvements.

The research, published June 20, 2026, in the Journal of the American Society of Nephrology and presented at the American Transplant Congress, marks the most extensive analysis to date of the attrition points in the kidney transplant continuum. These insights hold profound implications for policy frameworks, patient advocacy, and healthcare delivery models.

Addressing the entrenched social and systemic impediments to kidney transplantation demands coordinated efforts involving healthcare providers, payers, policymakers, and community stakeholders. Streamlining referral and evaluation protocols, augmenting support services, and ensuring resource availability at smaller centers—particularly in underserved regions—stand as imperatives.

NYU Langone Health’s funding and multidisciplinary team underscore the critical priority of tackling kidney transplant disparities with data-driven precision and commitment, aspiring to ensure that the lifesaving promise of transplantation reaches every eligible patient without undue delay or discrimination.

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Subject of Research: People
Article Title: Evaluating Barriers to Kidney Transplantation in the United States
News Publication Date: 20-Jun-2026
Keywords: Organ transplantation, Renal failure, Nephropathies, Health care delivery, Health disparity, Health equity

La réputation de la courgette n'est plus à faire : c'est l'un des légumes les plus productifs du potager. À tel point que certains jardiniers ne savent plus comment les cuisiner là où d’autres se demandent pourquoi leurs plants restent chétifs… Si vous faites partie de ces malchanceux, bonne...