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After pediatric liver transplantation (pLT), children undergo life-long immunosuppression since reliable biomarkers for the assessment of rejection probability are scarce. In the multicenter (n = 7) prospective clinical cohort "ChilSFree" study, we aimed to characterize longitudinal dynamics of soluble and cellular immune mediators during the first year after pLT and identify early biomarkers associated with outcome. Using a Luminex-based multiplex technique paired with flow cytometry, we characterized longitudinal dynamics of soluble immune mediators (SIMs, n = 50) and immune cells in the blood of 244 patients at eight visits over 1 year: before, and 7/14/21/28 days and 3/6/12 months after pLT. The unsupervised clustering of patients based on SIM profiles revealed six unique SIM signatures associated with clinical outcome. From three signatures linked to improved outcome, one was associated with 1-year-long rejection-free survival and stable graft function and was characterized by low levels of pro-inflammatory SIMs (CXCL8/9/10/12, CCL7, SCGF-β, sICAM-1), and high levels of regenerative (SCF, TNF-β) and pro-apoptotic (TRAIL) SIMs (all, p <0.001, fold change >100). Of note, this SIM signature appeared 2 weeks after pLT and remained stable over the entire year, pointing towards its potential as a novel early biomarker for minimizing or weaning immunosuppression. In the blood of these patients, a higher frequency of CD56bright natural killer cells (p <0.01), a known hallmark also associated with operationally tolerant pLT patients, was detected. The concordance of the model for prediction of rejection based on identified SIM signatures was 0.715, and 0.795, in combination with living-related transplantation as a covariate, respectively. SIM blood signatures may enable the non-invasive and early assessment of rejection risks in the first year after pLT, paving the way for improved clinical management. ChilSFree represents the largest pediatric liver transplant (pLT) cohort with paired longitudinal data on soluble immune mediators (SIMs) and immune phenotyping in the first year after pLT. SIM signatures allow for the selection of rejection-free patients 2 weeks after pLT independently of patient diagnosis, sex, or age. The SIM signatures may enable the non-invasive and early assessment of rejection risks, paving the way for minimization or withdrawal of immunosuppression after pLT. [Display omitted] • Early long-term predictive biomarkers for rejection-free survival post-pLT are missing. • Longitudinal SIM and immune phenotyping data up to 1-year post-pLT were acquired. • SIM signatures appearing 2 weeks post-pLT identify rejection-free patients. • SIM signatures can rank rejection risks and may facilitate optimization of immunosuppression. • Early intense immunosuppression may prevent development of favorable SIM signatures. [ABSTRACT FROM AUTHOR]

Ritonavir is a protease inhibitor initially developed for HIV treatment that is now used as a pharmacokinetic booster for other antiretrovirals due to it being a cytochrome P450 3A4 enzyme and P-glycoprotein inhibitor. Consequently, ritonavir is of special interest for repurposing in other diseases. It had an important role in battling the COVID-19 pandemic as a part of the developed drug Paxlovid® in association with nirmatrelvir and has shown effects in hepatitis and other pathogenic diseases. Ritonavir has also shown promising results in overcoming drug resistance and enhancing the efficacy of existing chemotherapeutic agents in oncology. Evidence of cancer repurposing potential was demonstrated in cancers such as ovarian, prostate, lung, myeloma, breast, and bladder cancer, with several mechanisms of action presented. In vitro studies indicate that ritonavir alone can inhibit key pathways involved in cancer cell survival and proliferation, causing apoptosis, cell cycle arrest, endoplasmic reticulum stress, and metabolic stress due to the inhibition of molecules like heat shock protein 90 and cyclin-dependent kinases. Ritonavir also causes resistant cells to become sensitized to anticancer drugs like gemcitabine or docetaxel. These findings indicate that repurposing ritonavir, either on its own or in combination with other medications, could be a promising approach for treating various diseases. This is particularly relevant in cancer therapy, where ritonavir repurposing is the central focus of this review. [ABSTRACT FROM AUTHOR]

Congenital microcoria (MCOR) is a rare hereditary developmental defect of the iris dilator muscle frequently associated with high axial myopia and high intraocular pressure (IOP) glaucoma. The condition is caused by submicroscopic rearrangements of chromosome 13q32.1. However, the mechanisms underlying the failure of iris development and the origin of associated features remain elusive. Here, we present a 3D architecture model of the 13q32.1 region, demonstrating that MCOR-related deletions consistently disrupt the boundary between two topologically associating domains (TADs). Deleting the critical MCOR-causing region in mice reveals ectopic Sox21 expression precisely aligning with Dct , each located in one of the two neighbor TADs. This observation is consistent with the TADs' boundary alteration and adoption of Dct regulatory elements by the Sox21 promoter. Additionally, we identify Tgfb2 as a target gene of SOX21 and show TGFΒ2 accumulation in the aqueous humor of an MCOR-affected subject. Accumulation of TGFB2 is recognized for its role in glaucoma and potential impact on axial myopia. Our results highlight the importance of SOX21-TGFB2 signaling in iris development and control of eye growth and IOP. Insights from MCOR studies may provide therapeutic avenues for this condition but also for glaucoma and high myopia conditions, affecting millions of people. [Display omitted] Congenital microcoria (MCOR) is a rare ocular developmental disease we attribute to pathological chromatin reorganization, ectopic Sox21 expression in the iris, and TGFB2 accumulation in the aqueous humor. This accumulation, known to trigger glaucoma and myopia, highlights novel pathways for treating these conditions, common in both MCOR and the general population. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is one of the leading causes of cancer deaths worldwide, even when found early in the disease, in both humans and dogs. Prostate cancer in dogs is common and is very similar to human prostate cancer, making them excellent models for comparative studies. Cannabidiol and Δ9-tetrahydrocannabinol are the two main components of Cannabis sativa and have been shown to have anti-cancer properties. In this study, extracts rich in cannabidiol or Δ9-tetrahydrocannabinol inhibited the growth of two canine prostate carcinoma cell lines. These results provide new information about the use of these natural compounds in canine models, which gives us the opportunity for further studies, both in the laboratory and in animals, to discover how these compounds act in the body, using dogs as a natural model for prostate carcinoma. Prostate cancer is one of the leading causes of cancer-related deaths worldwide, even when diagnosed at an early stage in humans and dogs. Dogs have a significant incidence of spontaneous prostate cancer, which is highly similar to human androgen-independent prostate cancer and represents a valuable model for comparative studies. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two main cannabinoids extracted from Cannabis sativa and have demonstrated antiproliferative and anti-invasive properties in different tumor types. In this study, CBD or THC-rich extracts inhibited the proliferation of two canine prostatic carcinoma cell lines, PC1 and PC2, showing an IC50 of 3.43 and 3.57 μM for CBD rich extracts, and 4.90 and 4.48 μM THC rich extracts, respectively. Cell death was also observed with both Annexin V and Propidium iodide staining for the canine cell lines. These results provide new information concerning the use of rich oil in canine PC and open a promising opportunity for further in vitro and in vivo studies to establish the mechanisms of action of these compounds using dogs as a natural model for prostatic carcinoma. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive and selective loss of dopaminergic (DAergic) neurons in the midbrain. The replacement of neuromelanin (NM)–containing DAergic neurons in the substantia nigra and the enhancement of NM concentration could offer a promising and safe approach to treating PD symptoms. The objective of this study was to investigate and compare the potential of human periapical-cysts mesenchymal stem cells (hPCy-MSCs) and dental pulp stem cells (DPSCs) to differentiate into DAergic NM-producing neurons and to generate functional 3-dimensional (3D) midbrain-like organoids in vitro. We assessed the changes in morphology and behavior of neuron-like cells (NLCs) as well as the expression of molecular markers characterizing the DAergic neurons. Furthermore, we observed electrically active and functionally mature DAergic neurons by means of electrophysiological assays, NM dosage assays, and the quantification of dopamine release by high-performance liquid chromatography. Our results demonstrate for the first time that both hPCy-MSCs and DPSCs are capable of differentiating into NLCs, further confirmed by the increase in lactate levels in the medium of cells exposed to neurogenic conditions. Importantly, we have induced such NLCs to further differentiate into functional DAergic NM-producing neurons. Finally, 3D midbrain-like organoids have been produced from oral stem cells: they appear as neurosphere-like structures diffusely expressing the neural marker β-III tubulin and containing NM-like granules. Our findings open up a novel and fascinating opportunity to rethink oral stem cells, and the derived 3D disease models, as a strategic and reliable tool for unveiling the neurodegenerative alterations. [ABSTRACT FROM AUTHOR]

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain's physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain's nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain's dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou's ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain's response to injury and pathology, embracing Malabou's concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice. [ABSTRACT FROM AUTHOR]

Patients with spinal cord injury (SCI) have permanent devastating motor and sensory disabilities. Secondary SCI is known for its complex progression and presents with sophisticated aberrant inflammation, vascular changes, and secondary cellular dysfunction, which aggravate the primary damage. Since their initial discovery, the potent neuroprotective effects and powerful delivery abilities of exosomes (Exos) have been reported in different research fields, including SCI. In this study, we summarize therapeutic advances related to the application of Exos in preclinical animal studies. Subsequently, we discuss the mechanisms of action of Exos derived from diverse cell types, including neurogenesis, angiogenesis, blood–spinal cord barrier preservation, anti-apoptosis, and anti-inflammatory potential. We also evaluate the relationship between the Exo delivery cargo and signaling pathways. Finally, we discuss the challenges and advantages of using Exos to offer innovative insights regarding the development of efficient clinical strategies for SCI. [ABSTRACT FROM AUTHOR]

Background: Burn trauma is one of the major causes of morbidity and mortality worldwide. The standard management of burn wounds consists of early debridement, dressing changes, surgical management, and split-thickness skin autografts (STSGs). However, there are limitations for the standard management that inclines us to find alternative treatment approaches, such as innovative cell-based therapies. We aimed to systematically review the different aspects of cell-based treatment approaches for burn wounds in clinical trials. Methods: A systematic search through PubMed, Medline, Embase, and Cochrane Library databases was carried out using a combination of keywords, including "Cell transplantation", "Fibroblast", "Keratinocyte", "Melanocyte", or "Stem Cell" with "Burn", "Burn wound", or "Burn injury". Firstly, titles and abstracts of the studies existing in these databases until "February 2024" were screened. Then, the selected studies were read thoroughly, and considering the inclusion and exclusion criteria, final articles were included in this systematic review. Moreover, a manual search was performed through the reference lists of the included studies to minimize the risk of missing reports. Results: Overall, 30 clinical trials with 970 patients were included in our study. Considering the type of cells, six studies used keratinocytes, nine used fibroblasts, eight used combined keratinocytes and fibroblasts, one study used combined keratinocytes and melanocytes, five used combined keratinocytes and fibroblasts and melanocytes, and one study used mesenchymal stem cells (MSCs). Evaluation of the preparation type in these studies showed that cultured method was used in 25 trials, and non-cultured method in 5 trials. Also, the graft type of 17 trials was allogeneic, and of 13 other trials was autologous. Conclusions: Our study showed that employing cell-based therapies for the treatment of burn wounds have significant results in clinical studies and are promising approaches that can be considered as alternative treatments in many cases. However, choosing appropriate cell-based treatment for each burn wound is essential and depends on the situation of each patient. [ABSTRACT FROM AUTHOR]

Precision Medicine (PM) is a transformative clinical medicine strategy that aims to revolutionize healthcare by leveraging biological information and biomarkers. In the context of maternal and neonatal health, PM enables personalized care from preconception through the postnatal period. Qatar has emerged as a key player in PM research, with dedicated programs driving advancements and translating cutting-edge research into clinical applications. This article delves into neonatal and maternal health in Qatar, emphasizing PM programs and initiatives that have been implemented. It also features noteworthy clinical cases that demonstrate the effectiveness of precision interventions. Furthermore, the article highlights the role of pharmacogenomics in addressing various maternal health conditions. The review further explores potential advancements in the application of PM in maternal and neonatal healthcare in Qatar. Article highlights Precision Medicine (PM) uses biological, lifestyle and environmental information including biomarkers for personalized care from preconception through the postnatal period. Qatar has become a significant player in PM research, with dedicated programs translating advanced research into clinical practice. Qatar's PM programs, including premarital genetic screening, newborn screening and reproductive medicine demonstrate significant progress and commitment. The article emphasizes the role of pharmacogenomics (PGx) in addressing maternal and neonatal health conditions. Anticipated integration of advanced multi-omics technologies and AI-driven predictive models into clinical practice. Continued evolution of pharmacogenomics to optimize drug therapies for pregnant women and neonates. Future efforts will focus on personalized interventions and improved healthcare outcomes for mothers and newborns in Qatar. [ABSTRACT FROM AUTHOR]

Ritonavir is a protease inhibitor initially developed for HIV treatment that is now used as a pharmacokinetic booster for other antiretrovirals due to it being a cytochrome P450 3A4 enzyme and P-glycoprotein inhibitor. Consequently, ritonavir is of special interest for repurposing in other diseases. It had an important role in battling the COVID-19 pandemic as a part of the developed drug Paxlovid® in association with nirmatrelvir and has shown effects in hepatitis and other pathogenic diseases. Ritonavir has also shown promising results in overcoming drug resistance and enhancing the efficacy of existing chemotherapeutic agents in oncology. Evidence of cancer repurposing potential was demonstrated in cancers such as ovarian, prostate, lung, myeloma, breast, and bladder cancer, with several mechanisms of action presented. In vitro studies indicate that ritonavir alone can inhibit key pathways involved in cancer cell survival and proliferation, causing apoptosis, cell cycle arrest, endoplasmic reticulum stress, and metabolic stress due to the inhibition of molecules like heat shock protein 90 and cyclin-dependent kinases. Ritonavir also causes resistant cells to become sensitized to anticancer drugs like gemcitabine or docetaxel. These findings indicate that repurposing ritonavir, either on its own or in combination with other medications, could be a promising approach for treating various diseases. This is particularly relevant in cancer therapy, where ritonavir repurposing is the central focus of this review.

Abstract Patients with spinal cord injury (SCI) have permanent devastating motor and sensory disabilities. Secondary SCI is known for its complex progression and presents with sophisticated aberrant inflammation, vascular changes, and secondary cellular dysfunction, which aggravate the primary damage. Since their initial discovery, the potent neuroprotective effects and powerful delivery abilities of exosomes (Exos) have been reported in different research fields, including SCI. In this study, we summarize therapeutic advances related to the application of Exos in preclinical animal studies. Subsequently, we discuss the mechanisms of action of Exos derived from diverse cell types, including neurogenesis, angiogenesis, blood–spinal cord barrier preservation, anti-apoptosis, and anti-inflammatory potential. We also evaluate the relationship between the Exo delivery cargo and signaling pathways. Finally, we discuss the challenges and advantages of using Exos to offer innovative insights regarding the development of efficient clinical strategies for SCI.

The field of cancer genomics and transcriptomics has evolved from targeted profiling to swift sequencing of individual tumor genome and transcriptome. The steady growth in genome, epigenome, and transcriptome datasets on a genome-wide scale has significantly increased our capability in capturing signatures that represent both the intrinsic and extrinsic biological features of tumors. These biological differences can help in precise molecular subtyping of cancer, predicting tumor progression, metastatic potential, and resistance to therapeutic agents. In this review, we summarized the current development of genomic, methylomic, transcriptomic, proteomic and metabolic signatures in the field of cancer research and highlighted their potentials in clinical applications to improve diagnosis, prognosis, and treatment decision in cancer patients.

Budapest Nephrology School (BNS) could have celebrated its 30th event if it had not been interrupted by COVID pandemic for a few years. Yet, the organization of 27th BNS in August 2023 resumed its successful and traditional activities at Semmelweis University, in the beautiful central European city of Budapest. In over two decades, BNS has faithfully adapted to the changes and developments of medical science and clinical nephrology, the fact which has kept it unique and attractive for nephrologists from across the globe. With such a long history and representing the top international professors of nephrology, BNS has proved to be a successful one-week, in-person refreshing course which has attracted over 1600 medical doctors from more than 60 countries. It has well served as an academic meeting point suitable for networking and exchange of up-to-date knowledge presented by the best international experts in nephrology. The dedication and focus of these experts on education, research and patient care represent the very concept of translational medicine. The invaluable experience of the past 27 years has set the standards for BNS to contribute to the evolution of translational nephrology in Europe in the next decade. [ABSTRACT FROM AUTHOR]

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enhancing its clinical translation. The momentum of cfDNA liquid biopsy technologies in recent years has propelled epigenetics to the forefront of molecular biology. We have only begun to reveal the true potential of epigenetics in both our understanding of disease and leveraging epigenetics in the diagnostic and therapeutic domains. Recent clinical applications of epigenetics-based cfDNA liquid biopsy revolve around DNA methylation in screening and early cancer detection, leading to the development of multi-cancer early detection tests and the capability to pinpoint tissues of origin. The clinical application of epigenetics in cfDNA liquid biopsy in minimal residual disease, monitoring, and surveillance are at their initial stages. A notable advancement in fragmentation patterns analysis has created a new avenue for epigenetic biomarkers. However, the widespread application of cfDNA liquid biopsy has many challenges, including biomarker sensitivity, specificity, logistics including infrastructure and personnel, data processing, handling, results interpretation, accessibility, and cost effectiveness. Exploring and translating epigenetics in cfDNA liquid biopsy technology can transform our understanding and perception of cancer prevention and management. cfDNA liquid biopsy has great potential in precision oncology to revolutionize conventional ways of early cancer detection, monitoring residual disease, treatment response, surveillance, and drug development. Adapting the implementation of liquid biopsy workflow to the local policy worldwide and developing point-of-care testing holds great potential to overcome global cancer disparity and improve cancer outcomes.

Abstract Background Fundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined ‘health weight’. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions. Methods The study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty. Results Principal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p

Abstract Background Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.

Intrinsic biological clocks drive the circadian rhythm, which coordinates the physiological and pathophysiological processes in the body. Recently, a bidirectional relationship between circadian rhythms and several neurological diseases has been reported. Neurological diseases can lead to the disruption of circadian homeostasis, thereby increasing disease severity. Therefore, optimizing the current treatments through circadian-based approaches, including adjusted dosing, changing lifestyle, and targeted interventions, offer a promising opportunity for better clinical outcomes and precision medicine. In this review, we provide detailed implications of the circadian rhythm in neurological diseases through bench-to-bedside approaches. Furthermore, based on the unsatisfactory clinical outcomes, we critically discuss the potential of circadian-based interventions, which may encourage more studies in this discipline, with the hope of improving treatment efficacy in neurological diseases. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated with KD, but also evaluates the possibility of using circulating endothelial injury biomarkers, such as circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tools for KD: a "liquid biopsy" approach. The challenges of translating liquid biopsies to use in KD and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostic tools is promising, and we hope this will be translated to clinical applications in the near future. [ABSTRACT FROM AUTHOR]

• Advancements in ischemic stroke research introduce new treatment challenges. • This narrative review selectively highlights advances with clinical impact using a fictional case. • Outstanding questions are addressed that can benefit from experimental-clinical research collaborations. Ischemic stroke research has enabled significant advancements in diagnosis, treatment, and management of this debilitating disease, yet challenges remain standing in the way of better patient prognoses. In this narrative review, a fictional case illustrates challenges and uncertainties that medical professionals still face – penumbra identification, lack of neuroprotective agents, side-effects of tissue plasminogen activator, dearth of molecular biomarkers, incomplete microvascular reperfusion or no-reflow, post-recanalization hyperperfusion, blood pressure management and procedural anesthetic effects. The current state of the field is broadly reviewed per topic, with the aim to introduce a broad audience (scientist and clinician alike) to recent successes in translational stroke research and pending scientific queries that are tractable for preclinical assessment. Opportunities for co-operation between clinical and experimental stroke experts are highlighted to increase the size and frequency of strides the field makes to improve our understanding of this disease and ways of treating it. [ABSTRACT FROM AUTHOR]

The ion channels Piezo 1 and Piezo 2 have been identified as membrane mechano-proteins. Studying mechanosensitive channels in chemosensory organs could help in understanding the mechanisms by which these channels operate, offering new therapeutic targets for various disorders. This study investigates the expression patterns of Piezo proteins in zebrafish chemosensory organs. For the first time, Piezo protein expression in adult zebrafish chemosensory organs is reported. In the olfactory epithelium, Piezo 1 immunolabels kappe neurons, microvillous cells, and crypt neurons, while Calretinin is expressed in ciliated sensory cells. The lack of overlap between Piezo 1 and Calretinin confirms Piezo 1's specificity for kappe neurons, microvillous cells, and crypt neurons. Piezo 2 shows intense immunoreactivity in kappe neurons, one-ciliated sensory cells, and multi-ciliated sensory cells, with overlapping Calretinin expression, indicating its olfactory neuron nature. In taste buds, Piezo 1 immunolabels Merkel-like cells at the bases of cutaneous and pharyngeal taste buds and the light and dark cells of cutaneous and oral taste buds. It also marks the dark cells of pharyngeal taste buds and support cells in oral taste buds. Piezo 2 is found in the light and dark cells of cutaneous and oral taste buds and isolated chemosensory cells. These findings provide new insights into the distribution of Piezo channels in zebrafish chemosensory organs, enhancing our understanding of their sensory processing and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Fundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined 'health weight'. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions. Methods: The study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty. Results: Principal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p < 0.05, identified differentially expressed genes (DEGs) in mouse and human datasets. DEGs were analysed further using area under curve (AUC) which identified 12 genes. Pathway enrichment analysis suggests these genes were involved in the biosynthesis and elongation of fatty acids and the transport, oxidation, and catabolic processing of lipids. qPCR validation found the majority of genes showed a tendency to be upregulated in joint tissues from obese participants. Three validated genes, IGFBP2 (p = 0.0363), DOK6 (0.0451) and CASP1 (0.0412) were found to be significantly different in obese joint tissues compared to lean-weight joint tissues. Conclusions: The present study has employed machine learning models across several published obesity datasets to identify obesity-associated genes which are validated in joint tissues from OA. These results suggest obesity-associated genes are conserved across conditions and may be fundamental in accelerating disease in obese individuals. Whilst further validations and additional conditions remain to be tested in this model, identifying obesity-associated genes in this way may serve as a global aid for patient stratification giving rise to the potential of targeted therapeutic interventions in such patient subpopulations. [ABSTRACT FROM AUTHOR]

The article discusses the field of translational pathology in drug discovery, which aims to combine disciplines and techniques to enhance prevention, diagnosis, and therapies. Translational pathology involves translating clinical data into basic research and applying knowledge gained from basic science research to clinical practice. The authors argue that translational pathology can improve the drug discovery process by helping to overcome obstacles and bridge the gap between basic research and clinical trials. They highlight the potential use of pathohistological evaluation in target validation, in vitro and in vivo screening, pharmacokinetic studies, and clinical trials. The article emphasizes the need to understand the limitations of animal models in relation to human disease and the importance of investigating the expression and function of target-expressing cell types in both naive tissue and disease models. The article also highlights the heterogeneity of tissue composition and cell types within tumor samples, which has implications for treatment outcomes. Pathological evaluation is suggested as a valuable tool for assessing drug distribution and understanding disease pathophysiology. The article concludes by discussing the role of translational pathology in personalized medicine and the identification of drug targets. The document provides a list of references from various scientific articles related to topics such as transgenic and gene knockout mouse models, integrins in cancer progression, personalized therapy selection, drug discovery and development, and the challenges of translational pathology. [Extracted from the article]

Background: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease. [ABSTRACT FROM AUTHOR]

Purpose: Artificial intelligence (AI) has emerged as a transformative force in medical research and is garnering increased attention in the public consciousness. This represents a critical time period in which medical researchers, healthcare providers, insurers, regulatory agencies, and patients are all developing and shaping their beliefs and policies regarding the use of AI in the healthcare sector. The successful deployment of AI will require support from all these groups. This commentary proposes that widespread support for medical AI must be driven by clear and transparent scientific reporting, beginning at the earliest stages of scientific research. Methods: A review of relevant guidelines and literature describing how scientific reporting plays a central role at key stages in the life cycle of an AI software product was conducted. To contextualize this principle within a specific medical domain, we discuss the current state of predictive tissue outcome modeling in acute ischemic stroke and the unique challenges presented therein. Results and Conclusion: Translating AI methods from the research to the clinical domain is complicated by challenges related to model design and validation studies, medical product regulations, and healthcare providers' reservations regarding AI's efficacy and affordability. However, each of these limitations is also an opportunity for high-impact research that will help to accelerate the clinical adoption of state-of-the-art medical AI. In all cases, establishing and adhering to appropriate reporting standards is an important responsibility that is shared by all of the parties involved in the life cycle of a prospective AI software product. [ABSTRACT FROM AUTHOR]

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain’s physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain’s nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain’s dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou’s ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain’s response to injury and pathology, embracing Malabou’s concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice.

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 “reprogrammed stem-like” state, marked by robust in vitro proliferation. This is achieved without reliance on exogenous gene expression or viral transfection, while maintaining the genetic profile of the parental cells. So far, CR technology has been used to study biology of diseases, targeted therapies (precision medicine), regenerative medicine, and noninvasive diagnosis and surveillance. Respiratory diseases, ranking as the third leading cause of global mortality, pose a significant burden to healthcare systems worldwide. Given the substantial mortality and morbidity rates of respiratory diseases, efficient and rapid preclinical models are imperative to accurately recapitulate the diverse spectrum of respiratory conditions. In this article, we discuss the applications and future potential of CR technology in modeling various respiratory tract diseases, including lung cancer, respiratory viral infections (such as influenza and Covid-19 and etc.), asthma, cystic fibrosis, respiratory papillomatosis, and upper aerodigestive track tumors. Furthermore, we discuss the potential utility of CR in personalized medicine, regenerative medicine, and clinical translation.

Budapest Nephrology School (BNS) could have celebrated its 30th event if it had not been interrupted by COVID pandemic for a few years. Yet, the organization of 27th BNS in August 2023 resumed its successful and traditional activities at Semmelweis University, in the beautiful central European city of Budapest. In over two decades, BNS has faithfully adapted to the changes and developments of medical science and clinical nephrology, the fact which has kept it unique and attractive for nephrologists from across the globe. With such a long history and representing the top international professors of nephrology, BNS has proved to be a successful one-week, in-person refreshing course which has attracted over 1600 medical doctors from more than 60 countries. It has well served as an academic meeting point suitable for networking and exchange of up-to-date knowledge presented by the best international experts in nephrology. The dedication and focus of these experts on education, research and patient care represent the very concept of translational medicine. The invaluable experience of the past 27 years has set the standards for BNS to contribute to the evolution of translational nephrology in Europe in the next decade.

Inflammation plays a critical role in conditions such as acute liver failure, acute-on-chronic liver failure, and ischemia–reperfusion-induced liver injury. Various pathogenic pathways contribute to liver inflammation, involving inflammatory polarization of macrophages and Küpffer cells, neutrophil infiltration, dysregulation of T cell subsets, oxidative stress, and activation of hepatic stellate cells. While mesenchymal stromal cells (MSCs) have demonstrated beneficial properties, their clinical translation is limited by their cellular nature. However, MSC-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach for immunomodulation. MSC-EVs naturally mirror their parental cell properties, overcoming the limitations associated with the use of MSCs. In vitro and in vivo preclinical studies have demonstrated that MSC-EVs replicate the beneficial effects of MSCs in liver injury. This includes the reduction of cell death and oxidative stress, improvement of hepatocyte function, induction of immunomodulatory effects, and mitigation of cytokine storm. Nevertheless, MSC-EVs face challenges regarding the necessity of defining consistent isolation methods, optimizing MSCs culture conditions, and establishing quality control measures for EV characterization and functional assessment. By establishing standardized protocols, guidelines, and affordable cost mass production, clinicians and researchers will have a solid foundation to conduct further studies, validate the therapeutic efficacy of MSC-EVs, and ultimately pave the way for their clinical implementation in acute liver injury. [ABSTRACT FROM AUTHOR]

Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non‐injectable, to clinical studies. In an article published in 2020 entitled “Hydrogels in the clinic”, we reviewed the clinical landscape and translational challenges of injectable hydrogels. Here, we provide an update on the advances in the field and also extend the scope to include non‐injectable hydrogels. We highlight recently approved hydrogel products, provide an update on the clinical trials of injectable hydrogels, and discuss active clinical trials of topically applied and implantable hydrogels. [ABSTRACT FROM AUTHOR]

Background: The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient‐derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine. Methods: We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient‐derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions. Results: In tumor development, the interaction between cellular and non‐cellular components in the tumor microenvironment (TME) has a crucial role. Co‐culture, Air‐liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis. Conclusion: An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer. [ABSTRACT FROM AUTHOR]

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Aim: Peripheral nerve injury regeneration studies using animal models are crucial to different pre-clinical therapeutic approaches efficacy evaluation whatever the surgical technique explored. Materials & methods: A 944 articles systematic review on 'peripheral nerve injury in animal models' over the last 9 years was carried out. Results: It was found that 91% used rodents, and only 9% employed large animals. Different nerves are studied, with generated gaps (10,78 mm) and methods applied for regeneration evaluation uniformed. Sciatic nerve was the most used (88%), followed by median and facial nerves (2.6%), significantly different. Conclusion: There has not been a significant scale-up of the in vivo testing to large animal models (anatomically/physiologically closer to humans), allowing an improvement in translational medicine for clinical cases. [ABSTRACT FROM AUTHOR]

Specific subpopulations of neurons in nerve and sensory systems must be developed and maintained, and this is accomplished in significant part by neurotrophins (NTs) and the signaling receptors on which they act, called tyrosine protein kinase receptors (Trks). The neurotrophins–tyrosine protein kinase receptors (NTs/Trks) system is involved in sensory organ regulation, including the visual system. An NTs/Trks system alteration is associated with neurodegeneration related to aging and diseases, including retinal pathologies. An emergent model in the field of translational medicine, for instance, in aging study, is the annual killifish belonging to the Nothobranchius genus, thanks to its short lifespan. Members of this genus, such as Nothobranchius guentheri, and humans share a similar retinal stratigraphy. Nevertheless, according to the authors' knowledge, the occurrence and distribution of the NTs/Trks system in the retina of N. guentheri has never been investigated before. Therefore, the present study aimed to localize neurotrophin BDNF, NGF, and NT-3 and TrkA, TrkB, and TrkC receptors in the N. guentheri retina using the immunofluorescence method. The present investigation demonstrates, for the first time, the occurrence of the NTs/Trks system in N. guentheri retina and, consequently, the potential key role of these proteins in the biology and survival of the retinal cells. [ABSTRACT FROM AUTHOR]

The concept of "translational bioethics" has received considerable attention in recent years. Most publications draw an analogy to translational medicine and describe bioethical research that aims at implementing and evaluating ethical interventions. However, current accounts of translational bioethics are often rather vague and seem to differ with regard to conceptual and methodological assumptions. It is not clear and scarcely analyzed what exactly "translation" in the field of bioethics means, in particular regarding goals and processes so that it is justified to appeal to translational medicine. In this article, we thus explore possible analogies and disanalogies between translational medicine and translational bioethics to establish whether the often occurring reference to concepts of translational medicine in the field of bioethics can be justified by substantial analogies. We will first provide an account of different models of translational medicine. In a second step, we will propose an analytic definition that explicitly articulates the essential characteristics of "translational research" irrespective of the research field (i.e., biomedicine, bioethics). Subsequently, we will explore whether and in how far general characteristics and phases of translational research in medicine can be applied to translational research in bioethics. Based on our analyses, we will come to the skeptical conclusion that at present there are considerable conceptual disanalogies and unsolved conceptual problems that disallow using "translational bioethics" in a meaningful analogy to respective accounts in biomedicine. Nevertheless, we will demonstrate that some insights gained by the conceptual accounts of translational medicine can contribute to advance current research activities in bioethics. [ABSTRACT FROM AUTHOR]

Nursing translational research (TR) begins with clinical discovery and medical research and leads to clinical application in patients. TR is key to improving nursing quality and developing the nursing profession. However, its development in China remains limited, and the reasons for this are unclear. We aim to enhance the recognition of nursing TR among nursing practitioners in China by exploring their cognition about nursing TR and associated influences. We distributed an internet-based questionnaire to 683 nursing practitioners between February 13 and March 15, 2023. We analyzed the characteristics and cognition of nursing TR using descriptive statistics, the chi-squared test, Fisher's exact test, the Wilcoxon rank-sum test, Kruskal–Wallis H test, and stepwise logistic regression analysis. The majority (79.65%) of nursing practitioners who responded to the questionnaire were willing to participate in nursing TR. Nursing practitioners with a higher educational level, stronger recognition of the importance of nursing TR, and stronger recognition of transdisciplinary nursing TR were more willing to participate in nursing TR. The results of this study can accelerate nursing practitioners' willingness to participate in nursing TR. We identified strategies to promote TR: provide further education, optimize courses in higher education, disseminate information, provide guidance on the importance of nursing TR, and establish a nursing TR platform with appropriate potential collaborators. • Participation in translational medical research (TMR) depends on education. • Nurses' willingness to practice TMR increases due to collaborative benefits. • Accelerating willingness to participate depends on opportunities to improve education. • Opportunities should include platform with transdisciplinary collaborators. [ABSTRACT FROM AUTHOR]

Background: Obesity is a complex metabolic disorder that is associated with several diseases. Recently, precision nutrition (PN) has emerged as a tailored approach to provide individualised dietary recommendations. Aim: This review discusses the major intrinsic and extrinsic components considered when applying PN during the management of obesity and common associated chronic conditions. Results: The review identified three main PN components: gene–nutrient interactions, intestinal microbiota, and lifestyle factors. Genetic makeup significantly contributes to inter-individual variations in dietary behaviours, with advanced genome sequencing and population genetics aiding in detecting gene variants associated with obesity. Additionally, PN-based host-microbiota evaluation emerges as an advanced therapeutic tool, impacting disease control and prevention. The gut microbiome's composition regulates diverse responses to nutritional recommendations. Several studies highlight PN's effectiveness in improving diet quality and enhancing adherence to physical activity among obese patients. PN is a key strategy for addressing obesity-related risk factors, encompassing dietary patterns, body weight, fat, blood lipids, glucose levels, and insulin resistance. Conclusion: PN stands out as a feasible tool for effectively managing obesity, considering its ability to integrate genetic and lifestyle factors. The application of PN-based approaches not only improves current obesity conditions but also holds promise for preventing obesity and its associated complications in the long term. [ABSTRACT FROM AUTHOR]

Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.

The expansion applications of semiconducting polymer dots (Pdots) among optical nanomaterial field have long posed a challenge for researchers, promoting their intelligent application in multifunctional nano-imaging systems and integrated nanomedicine carriers for diagnosis and treatment. Despite notable progress, several inadequacies still persist in the field of Pdots, including the development of simplified near-infrared (NIR) optical nanoprobes, elucidation of their inherent biological behavior, and integration of information processing and nanotechnology into biomedical applications. This review aims to comprehensively elucidate the current status of Pdots as a classical nanophotonic material by discussing its advantages and limitations in terms of biocompatibility, adaptability to microenvironments in vivo, etc. Multifunctional integration and surface chemistry play crucial roles in realizing the intelligent application of Pdots. Information visualization based on their optical and physicochemical properties is pivotal for achieving detection, sensing, and labeling probes. Therefore, we have refined the underlying mechanisms and constructed multiple comprehensive original mechanism summaries to establish a benchmark. Additionally, we have explored the cross-linking interactions between Pdots and nanomedicine, potential yet complete biological metabolic pathways, future research directions, and innovative solutions for integrating diagnosis and treatment strategies. This review presents the possible expectations and valuable insights for advancing Pdots, specifically from chemical, medical, and photophysical practitioners’ standpoints.

Lung cancer is one of the leading causes of death among all cancer deaths. This cancer is classified into two different histological subtypes: non-small cell lung cancer (NSCLC), which is the most common subtype, and small cell lung cancer (SCLC), which is the most aggressive subtype. Understanding the molecular characteristics of lung cancer has expanded our knowledge of the cellular origins and molecular pathways affected by each of these subtypes and has contributed to the development of new therapies. Traditional treatments for lung cancer include surgery, chemotherapy, and radiotherapy. Advances in understanding the nature and specificity of lung cancer have led to the development of immunotherapy, which is the newest and most specialized treatment in the treatment of lung cancer. Each of these treatments has advantages and disadvantages and causes side effects. Today, combination therapy for lung cancer reduces side effects and increases the speed of recovery. Despite the significant progress that has been made in the treatment of lung cancer in the last decade, further research into new drugs and combination therapies is needed to extend the clinical benefits and improve outcomes in lung cancer. In this review article, we discussed common lung cancer treatments and their combinations from the most advanced to the newest.

This document discusses the key concepts of translational research in the field of ophthalmology. Translational research aims to bridge the gap between existing knowledge and medical practice, with the goal of benefiting patients. It involves the transfer of diagnostic and therapeutic advances from the laboratory to clinical practice. The document explores the stakeholders of translational research, the scope of translational medicine, the components of translational research, barriers to its success, and future directions. It emphasizes the importance of collaboration and communication among different stakeholders to promote effective translational research. [Extracted from the article]