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Oleic acid activates TGFβ-Smad3 signaling to promote ovarian cancer progression.

BACKGROUND: Ovarian cancer represents the most aggressive and lethal gynecological cancer, frequently demonstrating a distinct propensity fo … eic acid treatment significantly enhanced proliferation of ovarian cancer cells and patient-derived organoids. Remarkably, oleic acid also increased membrane fluidity and promoted cell migration. Mechanistically, TGFβ-Smad3 signaling cascade is selectively activated by oleic acid, and inhibited by SCD1 suppression. Importantly, activation of Smad3 caused by …

Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.

The COVID-19 pandemic has revealed that the impact of SARS-CoV-2 infection extends well beyond the acute phase, with long-term sequelae affe … preclinical platforms, including patient-derived induced pluripotent stem cell (iPSC)-based cardiac organoids, engineered heart tissues, and organ-on-a-chip systems has enabled mechanistic dissection of Long COVID pathophysiology. These human-relevant models, when integrated with clinical datasets and artificial intelligence (AI)-driven analytics, offer pow …

Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.

BACKGROUND: Connexin (Cx) hemichannels (HCs) contribute to glioblastoma (GBM) progression by facilitating intercellular communication and releasing pro-tumorigenic molecules, including ATP and glutamate. METHODS: The efficacy of abEC1.1, a monoclonal antibody that inhibits Cx26, Cx30, and Cx32 HCs, was assessed in vitro by measuring invasion capability, dye and Ca2+ uptake, glutamate and ATP release in patient-derived GBM cultures or organoids. Adeno-associated virus (AAV)-mediated antibody gene delivery, or convection-enhanced delivery (CED) of the purified antibody, was used in vivo to test…

Rethinking Celiac Disease Management: Treatment Approaches Beyond the Gluten-Free Diet.

Celiac disease (CeD) is a chronic, immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals, with envi … roaches. More recently, advanced experimental and computational platforms, such as human intestinal organoids, organ-on-chip systems, and machine learning-driven analytics, are being leveraged in efforts to accelerate translational research and support the rational design of precision medicine approaches. This narrative review synthesizes current evidence f …

The Human Thyroid-Derived CI-huThyrEC Cell Line Expresses the Thyrotropin (TSH) Receptor and Thyroglobulin but Lacks Other Essential Characteristics of Thyroid Follicular Cells.

Background: Thyroid hormone synthesis requires the normal function of thyroid follicular cells and adequate nutritional intake of iodine. Fo … PCR (RT-PCR) in FRTL5, PCCL3, and Cl-huThyrEC cells. The latter were cultured as monolayers and as organoids in Matrigel. Iodide uptake was measured and compared among the cell lines. Results: Gene expression analysis reveals that Cl-huThyrEC cells express the thyroid-restricted transcription factors (PAX8, NKX2.1, FOXE1), the TSH receptor (TSHR), and thyr …

Genes linked to hearing and vestibular phenotypes in humans and mice: an interspecies systematic review.

Mouse models are relevant to study functionality of genes involved in human hearing and vestibular disorders; however, other pre-clinical models including organoids could be more suitable depending on the gene and its homology across species. While some mouse models replicate human hearing phenotypes, models for vestibular disorders like Meniere Disease (MD) are lacking. We aimed to identify genes associated with auditory and vestibular phenotypes (AVP) in humans and mice to prioritize candidate genes for further MD research. A systematic review was conducted extracting data from PubMed, Scopu…

Synergistic antiviral activity against human adenovirus through combination of itraconazole and brincidofovir.

BACKGROUND AND PURPOSE: Human adenovirus (HAdV) causes respiratory or gastrointestinal tract infections depending on the virus subtype. Whil … Ku-63794 on the production of infectious HAdV in A549 and Caco-2 cells as well as human intestinal organoids (HIOs). Additionally, we evaluated the benefit of a combination of these host-directed drugs with the direct-acting antiviral brincidofovir. KEY RESULTS: Pharmacological treatment with itraconazole significantly reduced virus titres in different in …

Централизованные интеграционные механизмы нейроваскулярной дисфункции и новые синергические терапевтические стратегии.

Нейроваскулярный блок (NVU) — высокоинтегрированный многоклеточный комплекс, состоящий из нейронов, астроцитов, микрогли, микроваскулярных эндотелиальных клеток мозга (BMEC), перицитов и внеклеточной матрицы (ECM). Он формирует структурную и функциональную основу мозгового барьера (ББД) и имеет решающее значение для поддержания гомеостаза мозга. Традиционные стратегии нейрозащиты, ориентированные на отдельные типы клеток, продемонстрировали ограниченную эффективность при заболеваниях центральной нервной системы (СНС), главным образом из-за пренебрежения сложным межклеточным перекрестком внутри

Совпадение в аннотации оригинала
The neurovascular unit (NVU) is a highly integrated multicellular complex composed of neurons, astrocytes, microglia, brain microvascular en … cal microenvironment imbalance. Additionally, we integrate emerging NVU models (co-culture systems, organoids, microfluidic chips, 3D bioprinting) with multi-omics technologies to establish a cross-scale dynamic research paradigm, and propose multicomponent coordinated regulatory strategies for NVU-targeted therapies. This framework aims to expand the under …

Iridium(III) carbene complexes as potent girdin inhibitors against metastatic cancers.

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative…

Acquisition of epithelial plasticity in human chronic liver disease.

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily o … velopmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K-AKT-mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in …

Modeling respiratory tract diseases for clinical translation employing conditionally reprogrammed cells.

Preclinical models serve as indispensable tools in translational medicine. Specifically, patient-derived models such as patient-derived xenografts (PDX), induced pluripotent stem cells (iPSC), organoids, and recently developed technique of conditional reprogramming (CR) have been employed to reflect the host characteristics of diseases. CR technology involves co-culturing epithelial cells with irradiated Swiss-3T3-J2 mouse fibroblasts (feeder cells) in the presence of a Rho kinase (ROCK) inhibitor, Y-27632. CR technique facilitates the rapid conversion of both normal and malignant cells into a…

Early Weaning Inhibits Intestinal Stem Cell Expansion to Disrupt the Intestinal Integrity of Duroc Piglets via Regulating the Keap1/Nrf2 Signaling.

There are different stress resistance among different breeds of pigs. Changes in intestinal stem cells (ISCs) are still unclear among variou … s in the jejunum were reduced significantly 3 days after weaning. And ex vivo jejunal crypt-derived organoids exhibited growth disadvantages in weaned Duroc piglets. Notably, the Keap1/Nrf2 signaling activities and the expression of HO-1 were significantly depressed in weaned Duroc piglets compared to Unweaned Duroc piglets. Thus, we can conclude that ISCs …

Impaired intestinal FXR signaling is involved in aberrant stem cell function leading to intestinal failure-associated liver disease in pediatric patients with short bowel syndrome.

Intestinal failure-associated liver disease (IFALD) is a serious complication of long-term parenteral nutrition in patients with short bowel … iptional factor activated by steroids and bile acids. In both surgical biopsies and patient-derived organoids (PDOs), SBS patients with IFALD represented lower population of LGR5+ cells and decreased FXR expression. Moreover, treatment with T-βMCA in PDOs (an antagonist for FXR) dose-dependently reduced the population of LGR5+ cells and the proliferation ra …

RUVBL1/2 Blockade Targets YTHDF1 Activity to Suppress m6A-Dependent Oncogenic Translation and Colorectal Tumorigenesis.

The N6-methyladenosine (m6A) RNA-binding protein YTHDF1 is frequently overexpressed in colorectal cancer and drives chemotherapeutic resista … paired the growth of YTHDF1-high colorectal cancer cells, patient-derived primary colorectal cancer organoids, and subcutaneous xenografts. Mechanistically, YTHFD1 and RUVBL1/2 formed a positive feedforward circuit to accelerate oncogenic translation. YTHDF1 bound to m6A-modified RUVBL1/2 mRNA to promote translation initiation and protein expression. Coimmu …

Enhancer of Zeste Homolog 2 Protects Mucosal Melanoma from Ferroptosis via the KLF14-SLC7A11 Signaling Pathway.

BACKGROUND: Mucosal melanoma (MM) is epidemiologically, biologically, and molecularly distinct from cutaneous melanoma. Current treatment strategies have failed to significantly improve the prognosis for MM patients. This study aims to identify therapeutic targets and develop combination strategies by investigating the mechanisms underlying the tumorigenesis and progression of MM. METHODS: We analyzed the copy number amplification of enhancer of zeste homolog 2 (EZH2) in 547 melanoma patients and investigated its correlation with clinical prognosis. Utilizing cell lines, organoids, and patien…

Immunosuppressive role of benzo[a]pyrene exposure in prostate cancer progression.

Epidemiological studies indicate that prostate cancer (PCa) is the second prevalent malignant tumor affecting men globally. Environmental po … t tumor model of BaP exposure mouse and found that can promote the proliferation of tumors in vivo. Organoids-driven by PCa patients showed higher growth rate under BaP exposure. Flow cytometric analysis demonstrated a remarkable decrease in CD4+ T and CD8+ T cell infiltration levels. Moreover, we identified four genes (Mdm2, Ar, Foxo1, Crebbp) were strongl …

Elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and rare mutations.

INTRODUCTION: The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome of people with Cystic Fibrosis (pwCF) with at least one F508del mutation. However, carriers of rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment. METHODS: In this observational study, we report the results of the compassionate use of ETI in 10 pwCF carriers of rare mutations after 2 months of treatment. Rectal organoids and short-term cultures of nasal epithelium obtained from rectal suction biopsies and na…

The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs.

Ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase inhibitors are in clinical trials. Here we explored the molecular pharmacolog … , and the PARP inhibitor talazoparib in various models including cancer cell lines, patient-derived organoids, and mouse xenograft models. Furthermore, we demonstrate that M1774 reverses chemoresistance to anticancer DDAs in cancer cells lacking SLFN11 expression, suggesting that SLFN11 can be utilized for patient selection in upcoming clinical trials.

Hyaluronic acid-conjugated methotrexate and 5-fluorouracil for targeted drug delivery.

The delivery of chemotherapeutical drugs via nanomaterials has become a focus of pharmaceutical research over several decades due to improve … ainst CD44 receptors. By using drugs to act on patient-derived colorectal, liver, and breast cancer organoids, the anticancer effect of the nanodrug was identified and verified. These results showed that the nanodrug system developed in this study may have great potential as a targeted therapy for cancer.

The molecular mechanisms of cardiac development and related diseases.

Cardiac development is a complex and intricate process involving numerous molecular signals and pathways. Researchers have explored cardiac development through a long journey, starting with early studies observing morphological changes and progressing to the exploration of molecular mechanisms using various molecular biology methods. Currently, advancements in stem cell technology and sequencing technology, such as the generation of human pluripotent stem cells and cardiac organoids, multi-omics sequencing, and artificial intelligence (AI) technology, have enabled researchers to understand the…