Culture Model Research Articles

Anti-neurofascin-155 antibody mediated a distinct phenotype of chronic inflammatory demyelinating polyradiculoneuropathy.

To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.

A ‘Cultural Models’ Approach to Psychotherapy for Refugees and Asylum Seekers: A Case Study from the UK

Despite the existence of significant research on the mental health care challenges of migrants, particularly refugees and asylum seekers, less attention has been paid to treatment approaches. We used a case study from the UK to look at the topic from a cultural models approach (which comes from cognitive anthropology) to analyse migrants’ experiences with mental health care. Twenty-five refugees and asylum seekers living in North East England and Northern Ireland were interviewed who had used at least six sessions of talking therapy during the last three years. Our results suggested that adopting a ‘cultural models’ approach, which offers a new conceptual and methodological framework of migrants’ experiences and their underlying schemas and expectations, would significantly contribute to building therapeutic alliances and provide relevant and appropriate treatments for migrant clients, particularly for unrecognised pre- and post-migration traumatic experiences.

Exploring EFL learners’ actions during the use of lecture materials in Chinese tertiary classrooms from a transactional view

Learners’ interaction with lecture materials has remained underexplored despite the growing body of studies on the use of materials. The current study explored the actions EFL learners employed during the use of lecture materials in tertiary classrooms in China through the lens of a transactional view. This empirical study involved forty-two students in two classes as well as two instructors enrolled in the Comprehensive English Course. Qualitative analysis revealed five levels of learner actions during interactions initiated by lectures: awareness, involvement, intervention, creation, and autonomy. The study further highlighted three factors that significantly influence these actions: learners’ intrinsic motivation to participate in classroom interactions, discourse space for participation, and the cultural model of learning. Pedagogical implications for enhancing learner autonomy and contributions during lecture materials use were discussed based on results.

Addressing Challenges and Promoting Development: Strategies for Health and Wellness Industry in Ethnic Regions

China has entered an aging society. In order to respond to the aging society, government departments have successively introduced various pension policies since 2013 with an attempt to mitigate the impact of the aging society. Under this context, the health and wellness industry came into being. However, the documents of the central department for the health and wellness industry are still lacking, the health care issues in ethnic region have received less attention, and there is no specific legal source for local governments and enterprises to follow. The purpose of this paper is to clarify the development of the health and wellness industry in ethnic region through literature analysis, to study the feasible path of the development of the health and wellness industry in ethnic region, and to provide suggestions. This study finds 40 representative papers on rural revitalization and health and wellness industry in the past three years through literature retrieval. We summarize the questions raised in the papers, analyzes and evaluates them, and finally proposes a conclusion. Findings show that the development of health and wellness industry in ethnic region lacks national level policies, and the details of local implementation are relatively weak. Moreover, in terms of the development path of the health and wellness industry in ethnic region, the integration model of health care, sports, culture and tourism seems to be a feasible direction. In addition, the development of health and wellness industry in ethnic region has a positive impact on rural revitalization. In other words, the development of health and wellness industry in ethnic region may have a high coupling effect with regional economy. Finally, this study provides some useful suggestions for government departments and subsequent research.

Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells

The transcription factor STAT3 is activated by multiple cytokines and other extrinsic factors. It plays a key role in immune and inflammatory responses and, when dysregulated, in tumourigenesis. STAT3 is also an indispensable mediator of the cell death process that occurs during post-lactational regression of the mammary gland, one of the most dramatic examples of physiological cell death in adult mammals. During this involution of the gland, STAT3 powerfully enhances the lysosomal system to efficiently remove superfluous milk-producing mammary epithelial cells via a lysosomal-mediated programmed cell death pathway. The lysosome is a membrane-enclosed cytoplasmic organelle that digests and recycles cellular waste, with an important role as a signalling centre that monitors cellular metabolism. Here, we describe key strategies for investigating the role of STAT3 in regulating lysosomal function using a mammary epithelial cell culture model system. These include protocols for lysosome enrichment and enzyme activity assays, in addition to microscopic analyses of the vesicular compartment in cell lines. Collectively, these approaches provide the tools to investigate multiple aspects of lysosome biogenesis and function, and to define both direct and indirect roles for STAT3.

P04 How fibroblasts and azathioprine prepare the soil for cutaneous squamous cell carcinoma

Abstract Introduction and aims DNA damage-inducing immunosuppressive drugs such as azathioprine (AZA) act synergistically with ultraviolet (UV)A radiation and photosensitize the skin of immunosuppressed individuals, such as organ transplant recipients. These individuals have an increased risk of developing cutaneous squamous cell carcinoma (cSCC). The specific combination of AZA and UVA causes oxidative DNA damage that leaves behind a characteristic mutational signature in tumour keratinocytes of patients treated with AZA. However, as UVA radiation can penetrate the dermis, the impact of AZA/UVA on cells of the tumour microenvironment, such as fibroblasts, also need to be addressed. Fibroblasts are crucial for cSCC development and progression as they can switch to a protumourigenic phenotype. Methods Cell viability and senescence assays were performed to investigate the impact of AZA in combination with or without UVA on neonatal (nonsun-exposed) and adult (sun-exposed) human dermal fibroblasts. In addition, the impact of AZA/UVA-treated fibroblasts on the clonal growth properties of different cSCC cell models was investigated using three-dimensional (co)culture models. Results We found that AZA and UVA synergistically reduce the viability of both UV-naïve neonatal and sun-exposed adult dermal fibroblasts. In addition, combined AZA and UVA treatments lead to an increased percentage of senescent fibroblasts. We hypothesize that the aberrant secretome of these senescent fibroblasts can impact the growth behaviour of tumour cells. In a soft agar assay, the more malignant cSCC cells (MET-1) formed more and larger clonal spheroids and were less dependent on growth factors compared with spheroids formed by premalignant (PM-1) keratinocytes. Conclusions AZA and UVA act synergistically and potentiate a UVA-induced senescent fibroblast phenotype. The changed characteristics of these fibroblasts can impact the stem cell-like properties from premalignant and malignant keratinocytes. Combining keratinocyte and fibroblast culture models enables us to study how AZA/UVA promote the initiation and progression of cSCC.

The Mode of Being of Popular Literature in the 20th Century

The article is devoted to the functioning of literature (and, more broadly, cultural texts) in popular circulation and the transformation of their role in the 20th century. The starting point for the analysis is the link between commercialisation (as an immanent feature of the ‘lowbrow’ circulation) and the artistic quality of the output that is part of it. The examples of the phenomena under discussion come from different linguistic milieux. This highlights the transnational nature of popular works, which feature invariant solutions to plots. In these two contradictory yet simultaneous tendencies can be observed: schematisation and de-schematisation, which renews conventionalised solutions. The author also emphasises the role of English-language works in the creation of figures of the collective imagination. Their presence in the minds of readers and the transformations they undergo with the development of industrial society and urbanisation processes can be traced from the late 19th century to the 1990s. That is why the 20th century — a period of intense expansion of popular culture — is a cohesive cultural entity with distinguishable individual periods. They are usually associated with socio-political crises, with stories becoming a cultural response to them and, at the same time, their artistic reception in the imaginarium communis. In addition, this is a time of technological progress, significantly affecting the distribution and media-based mediation of cultural texts in popular circulation. Literature has ceased to be a ‘separate phenomenon’ in it, hence the need to look at it as a part of a larger whole, with which it enters into various relationships. The domination of English-language output during the analysed period is associated with the global hegemony of the Anglo-American entertainment model. At the same time — in the works available to Polish-speaking readers — its ‘over-presence’ stems from the appearance after 1989 of a large number of translations, which have significantly influenced domestic pop-culture; moreover, their popularity in the reality of the free market economy has been determined by the read- ers themselves with their purchasing choices. It is hard to speak in this situation of the existence of national models of popular culture, although undeniably there are authors who dominate the local publishing markets. And yet they, too, exist in the context of the global pop culture industry.

Cultural Competence Interventions in European Healthcare: A Scoping Review

Europe is undergoing rapid social change and is distinguished by its cultural superdiversity. Healthcare is facing an increasing need for professionals to adapt to this environment. Thus, the promotion of cultural competence in healthcare has become a priority. However, the training being developed and their suitability for the European context are not well known. The aim of this qualitative study has been to map the scientific literature in order to comprehend the current state of research on this topic. For this purpose, we conducted a systematic scoping review of the empirical publications focused on cultural competence interventions for healthcare professionals in European countries. The search was conducted in eight thematic (PsycINFO, MedLine, and PubPsych) and multidisciplinary databases (Academic Search Ultimate, E-Journals, Scopus, ProQuest, and Web of Science) to identify relevant publications up to 2023. Results were presented qualitatively. Out of the initial 6506 records screened, a total of 63 publications were included. Although the interventions were implemented in 23 different European countries, cultural competence interventions have not been widely adopted in Europe. Significant heterogeneity was observed in the conception and operacionalización of cultural competence models and in the implementation of the interventions. The interventions have mostly aimed at improving healthcare for minority population groups and have focused on the racial and ethnic dimensions of the individual. Future research is needed to contribute to the conceptual development of cultural competence to design programs tailored to European superdiversity. This scoping review has been registered in OSF and is available for consultation.

Apple pomace extract: photochemopreventive action against UVA radiation in a cell culture model

Apple pomace, a byproduct from juice industry, can be used as a valuable nutraceutical, hence its phenolic compounds, including rutin, are powerful antioxidants. This work evidence the extract enriched with apple polyphenols from apple pomace using ethanol: water as solvent and partitioned with ethyl acetate (1:1 w/w), where its lyophilized product was evaluated for its photochemopreventive action on MRC-5 fibroblasts against a harmful UVA radiation dose. The enriched apple pomace extract was able to promote photochemopreventive action against UVA radiation, decreasing cell death and the lipid peroxidation formation. Therefore, the optimized extraction process may make the apple pomace application viable as a source of bioactive extracts with photochemopreventive action against ultraviolet radiation to the use in dermal formulations.

P16 Fibroblast signalling crosstalk drives junctional epidermolysis bullosa disease progression

Abstract Introduction and aims Junctional epidermolysis bullosa (JEB) is a devastating hereditary skin disorder characterized by severe fragility of skin and mucus membrane, emerges as blistering with little or no trauma. The major classification of JEB includes JEB intermediate and JEB severe; the latter is the most common subtype, which is the result of loss of function mutations in the skin basement membrane protein laminin-332. Lacking this protein impairs basement membrane adhesion of epidermal keratinocytes and leads to deregulated epidermal–dermal crosstalk. The skin dermis is composed of multiple fibroblast subpopulations with different functions in skin homeostasis and repair; however, their specific involvement in skin diseases is largely unknown. Here, we investigate how fibroblast subpopulations, namely papillary and reticular fibroblasts, impact JEB disease progression and skin regeneration. Methods Three-dimensional (3D) organotypic (OT) combining healthy (control) and diseased (JEB) keratinocytes cells with distinct fibroblast subpopulations from different anatomical sites were developed and analysed by immunohistochemistry and RNA-Seq. Results JEB OTs with papillary fibroblasts showed increased epidermal growth, invagination of basal layer and deregulated differentiation compared with reticular fibroblasts. RNA-Seq analysis revealed altered activity in key signalling including immune, cytokine, gap junction, mitogen-activated protein kinase and remodelling of keratinization and ECM proteins, particularly in JEB OT cultured with papillary fibroblast. JEB OTs and cells also demonstrated variation in cell proliferation and activation of transforming growth factor-β1 and immune cell signalling. Currently, we are targeting identified signalling pathways in our two-dimensional and 3D cell culture models and identifying druggable targets, before testing selected candidates in our JEB mouse disease model for further preclinical validation. Conclusions By dissecting the pathological signalling interactions between keratinocytes and distinct fibroblast subpopulations, our goal is to identify new therapeutic target to improve the skin health and regeneration in patients with JEB.

Abstract A019: TRIM29 enhances the invasion of bladder cancer cells by modulating the intermediate filament network and focal adhesions

Abstract Background: Bladder cancer patient treatment and outcomes are determined by the tumor’s ability to invade and metastasize. Our previous work has shown that TRIM29, also known as ATDC, is regulated by TP63 in basal bladder cancers, where it promotes cancer invasion and metastasis. We also observe that TRIM29 predominately localizes to intermediate filaments in invasive bladder cancer cells. Hypothesis: TRIM29 promotes the invasive progression of bladder cancer by regulating K14-containing intermediate filaments and focal adhesions. Methods: To test this hypothesis, we utilized cell culture models of bladder cancer, live cell imaging and 2D and 3D invasion assays to examine the role of TRIM29 in the regulation of K14, focal adhesions and the migration and invasion and bladder cancer cells. Results: We observed a physical interaction between TRIM29 and K14 filamentous structures in bladder cancer cells. We also found that TRIM29 and K14 regulate focal adhesion stability during bladder cancer invasion. Finally, we found that both K14 and the focal adhesion protein, zyxin (ZYX), are essential for bladder cancer migration and invasion, acting downstream of TRIM29. Conclusions: Our findings highlight a novel role for TRIM29 in regulating the cytoskeleton and focal adhesion dynamics during tumor cell invasion and suggest a potential therapeutic pathway for treating bladder cancer. Citation Format: Yin Wang, Nicole A. Jerome, Allan Kelleher, Marian L. Henderson, Mark Day, Pierre A. Coulombe, Phillip L. Palmbos. TRIM29 enhances the invasion of bladder cancer cells by modulating the intermediate filament network and focal adhesions [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A019.

Cellular resolution contributions to ictal population signals.

The increased amplitude of ictal activity is a common feature of epileptic seizures, but the determinants of this amplitude have not been identified. Clinically, ictal amplitudes are measured electrographically (using, e.g., electroencephalography, electrocorticography, and depth electrodes), but these methods do not enable the assessment of the activity of individual neurons. Population signal may increase from three potential sources: (1) increased synchrony (i.e., more coactive neurons); (2) altered active state, from bursts of action potentials and/or paroxysmal depolarizing shifts in membrane potential; and (3) altered subthreshold state, which includes all lower levels of activity. Here, we quantify the fraction of ictal signal from each source. To identify the cellular determinants of the ictal signal, we measured single cell and population electrical activity and neuronal calcium levels via optical imaging of the genetically encoded calcium indicator (GECI) GCaMP. Spontaneous seizure activity was assessed with microendoscopy in an APP/PS1 mouse with focal cortical injury and via widefield imaging in the organotypic hippocampal slice cultures (OHSCs) model of posttraumatic epilepsy. Single cell calcium signals were linked to a range of electrical activities by performing simultaneous GECI-based calcium imaging and whole-cell patch-clamp recordings in spontaneously seizing OHSCs. Neuronal resolution calcium imaging of spontaneous seizures was then used to quantify the cellular contributions to population-level ictal signal. The seizure onset signal was primarily driven by increased subthreshold activity, consistent with either barrages of excitatory postsynaptic potentials or sustained membrane depolarization. Unsurprisingly, more neurons entered the active state as seizure activity progressed. However, the increasing fraction of active cells was primarily driven by synchronous reactivation and not from continued recruitment of new populations of neurons into the seizure. This work provides a critical link between single neuron activity and population measures of seizure activity.

Impact of CDK Inhibitors on TBXT Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma

Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the TBXT gene, resulting in detectable nuclear amounts of its gene product brachyury. This T-Box transcription factor is commonly recognised as being essential in chordoma cells, and limiting TBXT expression is thought to be the key factor in controlling this tumour. Although the tumour is rare, distinct molecular differences and vulnerabilities have been described with regard to its location and the progression status of the disease, rendering it mandatory for novel cell lines to reflect all relevant chordoma subtypes. Here, we describe a novel chordoma cell line arising from the pleural effusion of a disseminated, poorly differentiated chordoma. This cell line, U-CH22, represents a highly aggressive terminal chordoma and, therefore, fills a relevant gap within the panel of available cell culture models for this orphan disease. CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum.

Porcine lung tissue slices: a culture model for PRCV infection and innate immune response investigations

Respiratory coronaviruses (RCoVs) significantly threaten human health, necessitating the development of an ex vivo respiratory culture system for investigating RCoVs infection. Here, we successfully generated a porcine precision-cut lung slices (PCLSs) culture system, containing all resident lung cell types in their natural arrangement. Next, this culture system was inoculated with a porcine respiratory coronavirus (PRCV), exhibiting clinical features akin to humans who were infected by SARS-CoV-2. The results demonstrated that PRCV efficiently infected and replicated within PCLSs, targeting ciliated cells in the bronchioles, terminal bronchioles, respiratory bronchioles, and pulmonary alveoli. Additionally, through RNA-Seq analysis of the innate immune response in PCLSs following PRCV infection, expression levels of interferons, inflammatory cytokines and IFN stimulated genes were significantly upregulated. This ex vivo model may not only offer new insights into PRCV infection in the porcine respiratory tract but also serve as a valuable tool for studying human respiratory CoVs infection.

Reversibility of Endoplasmic Reticulum Stress Markers During Long-Term Glucose Starvation in Astrocytes

Previous studies have demonstrated a brain volume decrease linked to long-term starvation in patients with anorexia nervosa (AN). Food intake is critically diminished in this disorder, leading to one of the highest mortality rates within the psychiatric disease spectrum. As reported in animal models, astrocytes seem to be the most affected cell type in AN. In a recently established primary cell culture model, an elevated unfolded protein response (UPR) was observed in long-term glucose semi-starved astrocytes. A well-functioning protein machinery is essential for every cell, and prolonged UPR will lead to cell death. As a nucleic acid stress-sensing pathway with the activator located in the endoplasmic reticulum, the regulation of the cGAS-STING pathway (cyclic GMP-AMP synthase/stimulator of interferon genes) was additionally investigated in the starvation context. In the current study, a glucose semi-starvation protocol of 15 days, during which cells were supplied with 2 mM glucose in the medium, was prolonged with an additional 6-day long recovery period. Our findings showed that increased UPR mRNA expression was reversible after re-establishing the standard glucose concentration of 25 mM. Furthermore, we were able to verify the presence of cGAS and STING in astrocytes with a characteristic presence of cGAS in the astrocyte nucleus during starvation. A correlation between STING and the glial fibrillary acidic protein (GFAP) could be established, hinting at a conditional presence of STING with a specific astrocyte phenotype.Graphical

In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells

Background: The identification of novel therapeutic strategies for ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with the cysteine-dependent deubiquitinating enzyme (DUB) UCHL5, thus affecting the ubiquitin-proteasome-dependent degradation of proteins. Methods: 2c phenotypic/molecular effects were studied in two OC 2D/3D culture models and in a mouse xenograft model. Furthermore, we propose an in silico model of 2c interaction with DUB-UCHL5. Finally, we have tested the effect of 2c conjugated to several linkers to generate 2c/derivatives usable for improved drug delivery. Results: 2c effectively impairs the OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs proteasome activity and triggers apoptosis, most likely by interacting with DUB-UCHL5. We also propose a mechanism for the interaction with DUB-UCHL5 via an in silico evaluation of the enzyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcription factor E2F1. Eventually, 2c activity is often retained after the conjugation with linkers. Conclusion: Our data strongly support the potential therapeutic value of 2c/derivatives in OC.

Hypersensitive blood vessels in Clarkson disease.

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare, recurrent condition with dramatically increased blood vessel permeability and, therefore, induction of systemic edema, which may lead to organ damage and death. In this issue of the JCI, Ablooglu et al. showed that ISCLS vessels were hypersensitive to agents known to increase vascular permeability, using human biopsies, cell culture, and mouse models. Several endothelium-specific proteins that regulate endothelial junctions were dysregulated and thereby compromised the vascular barrier. These findings suggest that endothelium-intrinsic dysregulation underlies hyperpermeability and implicate the cytoplasmic serine/threonine protein phosphatase 2A (PP2A) as a potential drug target for the treatment of ISCLS.

HiPSC-derived macrophages improve drug sensitivity and selectivity in a macrophage-incorporating organoid culture model.

Accurate simulation of different cell type interactions is crucial for physiological and precise in vitro drug testing. Human tissue-resident macrophages are critical for modulating disease conditions and drug-induced injuries in various tissues; however, their limited availability has hindered their use in in vitro modeling. Therefore, this study aimed to create macrophage-containing organoid co-culture models by directly incorporating hiPSC-derived pre-macrophages into organoid and scaffold cell models. The fully differentiated cells in these organoids exhibited functional characteristics of tissue-resident macrophages with enriched pan-macrophage markers and the potential for M1/M2 subtype specialization upon cytokine stimulation. In a hepatic organoid model, the integrated macrophages replicated typical intrinsic properties, including cytokine release, polarization, and phagocytosis, and the co-culture model was more responsive to drug-induced liver injury than a macrophage-free model. Furthermore, alveolar organoid models containing these hiPSC-derived macrophages also showed increased drug and chemical sensitivity to pulmonary toxicants. Moreover, 3D adipocyte scaffold models incorporating macrophages effectively simulated in vivo insulin resistance observed in adipose tissue and showed improved insulin sensitivity on exposure to anti-diabetic drugs. Overall, the findings demonstrated that incorporating hiPSC-derived macrophages into organoid culture models resulted in more physiological and sensitive in vitro drug evaluation and screening systems.&#xD.

Carboplatin restricts peste des petits ruminants virus replication by suppressing the STING-mediated autophagy

Peste des petits ruminants virus (PPRV) is a morbillivirus that causes the acute and highly pathogenic infectious disease peste des petits ruminants (PPR) in small ruminants and poses a major threat to the goat and sheep industries. Currently, there is no effective treatment for PPRV infection. Here, we propose Carboplatin, a platinum-based regimen designed to treat a range of malignancies, as a potential antiviral agent. We showed that Carboplatin exhibits significant antiviral activity against PPRV in a cell culture model. The mechanism of action of Carboplatin against PPRV is mainly attributed to its ability to block STING mediated autophagy. Together, our study supports the discovery of Carboplatin as an antiviral against PPRV and potentially other closely related viruses, sheds light on its mode of action, and establishes STING as a valid and attractive target to counteract viral infection.

Basic models to advanced systems: harnessing the power of organoids-based microphysiological models of the human brain.

Understanding the complexities of the human brain's function in health and disease is a formidable challenge in neuroscience. While traditional models like animals offer valuable insights, they often fall short in accurately mirroring human biology and drug responses. Moreover, recent legislation has underscored the need for more predictive models that more accurately represent human physiology. To address this requirement, human-derived cell cultures have emerged as a crucial alternative for biomedical research. However, traditional static cell culture models lack the dynamic tissue microenvironment that governs human tissue function. Advanced in vitro systems, such as organoids and Microphysiological systems (MPS), bridge this gap by offering more accurate representations of human biology. Organoids, which are three-dimensional miniaturized organ-like structures derived from stem cells, exhibit physiological responses akin to native tissues, but lack essential tissue-specific components such as functional vascular structures and immune cells. Recent endeavors have focused on incorporating endothelial cells and immune cells into organoids to enhance vascularization, maturation, and disease modeling. MPS, including organ-on-chip technologies, integrate diverse cell types and vascularization under dynamic culture conditions, revolutionizing brain research by bridging the gap between in vitro and in vivo models. In this review, we delve into the evolution of MPS, with a particular focus on highlighting the significance of vascularization in enhancing the viability, functionality, and disease modeling potential of organoids. By examining the interplay of vasculature and neuronal cells within organoids, we can uncover novel therapeutic targets and gain valuable insights into disease mechanisms, offering the promise of significant advancements in neuroscience and improved patient outcomes.&#xD.