-
BioRxiv : the Preprint Server For... Jun 2024The spatial arrangement of cells is vital in developmental processes and organogenesis in multicellular life forms. Deep learning models trained with spatial omics data...
The spatial arrangement of cells is vital in developmental processes and organogenesis in multicellular life forms. Deep learning models trained with spatial omics data uncover complex patterns and relationships among cells, genes, and proteins in a high-dimensional space, providing new insights into biological processes and diseases. State-of-the-art spatial multi-cell gene expression methods using histological images of tissue stained with hematoxylin and eosin (H&E) to characterize cellular heterogeneity. These computational techniques offer the advantage of analyzing vast amounts of spatial data in a scalable and automated manner, thereby accelerating scientific discovery and enabling more precise medical diagnostics and treatments. In this work, we developed a vision transformer (ViT) framework to map histological signatures to spatial single-cell transcriptomic signatures, named SPiRiT ( S patial Omics P rediction and R eproducibility integrated T ransformer). Our framework was enhanced by integrating cross validation with model interpretation during hyper-parameter tuning. SPiRiT predicts single-cell spatial gene expression using the matched histopathological image tiles of human breast cancer and whole mouse pup, evaluated by Xenium (10x Genomics) datasets. Furthermore, ViT model interpretation reveals the high-resolution, high attention area (HAR) that the ViT model uses to predict the gene expression, including marker genes for invasive cancer cells ( ), stromal cells ( ), and lymphocytes ( ). In an apple-to-apple comparison with the ST-Net Convolutional Neural Network algorithm, SPiRiT improved predictive accuracy by 40% using human breast cancer Visium (10x Genomics) dataset. Cancer biomarker gene prediction and expression level are highly consistent with the tumor region annotation. In summary, our work highlights the feasibility to infer spatial single-cell gene expression using tissue morphology in multiple-species, i.e., human and mouse, and multi-organs, i.e., mouse whole body morphology. Importantly, incorporating model interpretation and vision transformer is expected to serve as a general-purpose framework for spatial transcriptomics.
PubMed: 38915550
DOI: 10.1101/2024.06.12.598686 -
Journal of Orthopaedic Surgery and... Jun 2024The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using... (Meta-Analysis)
Meta-Analysis
PURPOSE
The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate.
METHODS
We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted.
RESULTS
A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = - 2.825, 95% CI - 3.343 to - 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8-15%), with a total of 12 patients experiencing complications.
CONCLUSION
The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice.
Topics: Humans; Talus; Chondrogenesis; Transplantation, Autologous; Treatment Outcome; Time Factors; Cartilage, Articular
PubMed: 38915104
DOI: 10.1186/s13018-024-04864-z -
PloS One 2024The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the...
The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process. In this study, we describe the effect of taurine acting via the ionotropic GABAA receptor and the metabotropic GABAB receptor on the neuronal differentiation and electrophysiological properties of precursor cells derived from the subventricular zone of the mouse brain. Taurine stimulates the number of neurites and favors the dendritic complexity of the neural precursor cells, accompanied by changes in the somatic input resistance and the strength of inward and outward membranal currents. At the pharmacological level, the blockade of GABAA receptors inhibits these effects, whereas the stimulation of GABAB receptors has no positive effects on the taurine-mediated differentiation process. Strikingly, the blockade of the GABAB receptor with CGP533737 stimulates neurite outgrowth, dendritic complexity, and membranal current kinetics of neural precursor cells. The effects of taurine on the differentiation process involve Ca2+ mobilization and the activation of intracellular signaling cascades since chelation of intracellular calcium with BAPTA-AM, and inhibition of the CaMKII, ERK1/2, and Src kinase inhibits the neurite outgrowth of neural precursor cells of the subventricular zone.
Topics: Animals; Neural Stem Cells; Receptors, GABA-B; Mice; Cell Differentiation; Receptors, GABA-A; Lateral Ventricles; Taurine; Neurogenesis; Calcium
PubMed: 38913632
DOI: 10.1371/journal.pone.0305853 -
International Journal of Nanomedicine 2024Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a...
BACKGROUND
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR TItpr3/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.
METHODS
Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.
RESULTS
Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX and SOX2/GFAP cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.
CONCLUSION
In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.
Topics: Animals; Mice, Inbred C57BL; Mice; Fullerenes; Autism Spectrum Disorder; Cognitive Dysfunction; Disease Models, Animal; Male; Doublecortin Protein; Social Behavior; Behavior, Animal; Hippocampus; Vascular Endothelial Growth Factor A; Neuroprotective Agents; Neurogenesis; Autistic Disorder
PubMed: 38911505
DOI: 10.2147/IJN.S459511 -
Frontiers in Pharmacology 2024The members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the...
INTRODUCTION
The members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates.
OBJECTIVE
This study's main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients.
METHODOLOGY
investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells.
RESULTS
Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through and study.
DISCUSSION
Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.
PubMed: 38910889
DOI: 10.3389/fphar.2024.1361679 -
Biochemistry and Biophysics Reports Sep 2024The three-dimensional (3D) kidney organoid is a breakthrough model for recapitulating renal morphology and function , which is grown from stem cells and resembles... (Review)
Review
The three-dimensional (3D) kidney organoid is a breakthrough model for recapitulating renal morphology and function , which is grown from stem cells and resembles mammalian kidney organogenesis. Currently, protocols for cultivating this model from induced pluripotent stem cells (iPSCs) and patient-derived adult stem cells (ASCs) have been widely reported. In recent years, scientists have focused on combining cutting-edge bioengineering and bioinformatics technologies to improve the developmental accuracy of kidney organoids and achieve high-throughput experimentation. As a remarkable tool for mechanistic research of the renal system, kidney organoid has both potential and challenges. In this review, we have described the evolution of kidney organoid establishment methods and highlighted the latest progress leading to a more sophisticated kidney transformation research model. Finally, we have summarized the main applications of renal organoids in exploring kidney disease.
PubMed: 38910872
DOI: 10.1016/j.bbrep.2024.101736 -
Journal of Nanobiotechnology Jun 2024Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our...
Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.
Topics: Animals; Autophagy; Mice; Exosomes; MicroRNAs; Cold Temperature; Osteogenesis; Mice, Inbred C57BL; Mesenchymal Stem Cells; Osteoporosis; Cell Differentiation; Bone and Bones; Female; Bone Density; Sirolimus
PubMed: 38910236
DOI: 10.1186/s12951-024-02640-z -
Neural Development Jun 2024The complex morphology of neurons requires precise control of their microtubule cytoskeleton. This is achieved by microtubule-associated proteins (MAPs) that regulate...
The complex morphology of neurons requires precise control of their microtubule cytoskeleton. This is achieved by microtubule-associated proteins (MAPs) that regulate the assembly and stability of microtubules, and transport of molecules and vesicles along them. While many of these MAPs function in all cells, some are specifically or predominantly involved in regulating microtubules in neurons. Here we use the sea anemone Nematostella vectensis as a model organism to provide new insights into the early evolution of neural microtubule regulation. As a cnidarian, Nematostella belongs to an outgroup to all bilaterians and thus occupies an informative phylogenetic position for reconstructing the evolution of nervous system development. We identified an ortholog of the microtubule-binding protein doublecortin-like kinase (NvDclk1) as a gene that is predominantly expressed in neurons and cnidocytes (stinging cells), two classes of cells belonging to the neural lineage in cnidarians. A transgenic NvDclk1 reporter line revealed an elaborate network of neurite-like processes emerging from cnidocytes in the tentacles and the body column. A transgene expressing NvDclk1 under the control of the NvDclk1 promoter suggests that NvDclk1 localizes to microtubules and therefore likely functions as a microtubule-binding protein. Further, we generated a mutant for NvDclk1 using CRISPR/Cas9 and show that the mutants fail to generate mature cnidocytes. Our results support the hypothesis that the elaboration of programs for microtubule regulation occurred early in the evolution of nervous systems.
Topics: Animals; Sea Anemones; Neurons; Doublecortin-Like Kinases; Protein Serine-Threonine Kinases; Microtubules; Neurogenesis; Animals, Genetically Modified; Microtubule-Associated Proteins
PubMed: 38909268
DOI: 10.1186/s13064-024-00188-0 -
Neural Development Jun 2024Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the... (Review)
Review
Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this 'superficial' simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction.
Topics: Animals; Nervous System; Neurogenesis; Platyhelminths; Biological Evolution; Neurons
PubMed: 38907301
DOI: 10.1186/s13064-024-00187-1 -
Journal of Ovarian Research Jun 2024Teratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a...
Amplifications of EVX2 and HOXD9-HOXD13 on 2q31 in mature cystic teratomas of the ovary identified by array comparative genomic hybridization may explain teratoma characteristics in chondrogenesis and osteogenesis.
BACKGROUND
Teratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a better understanding of their stepwise differentiation processes and molecular bases, which could prove useful for the development of tissue-engineering technologies.
METHODS
In the present study, we analyzed the copy number aberrations of nine ovarian mature cystic teratomas using array comparative genomic hybridization in an attempt to reveal their genomic aberrations.
RESULTS
The many chromosomal aberrations observed on array comparative genomic hybridization analysis reveal the complex genetics of this tumor. Amplifications and deletions of large DNA fragments were observed in some samples, while amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, NDUFV1 on 11q13.2, and RPL10, SNORA70, DNASE1L1, TAZ, ATP6AP1, and GDI1 on Xq28 were found in all nine mature cystic teratomas.
CONCLUSIONS
Our results indicated that amplifications of these genes may play an important etiological role in teratoma formation. Moreover, amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, found on array comparative genomic hybridization, may help to explain the characteristics of teratomas in chondrogenesis and osteogenesis.
Topics: Humans; Female; Teratoma; Comparative Genomic Hybridization; Ovarian Neoplasms; Transcription Factors; Homeodomain Proteins; Osteogenesis; Chondrogenesis; Adult; Middle Aged; Neoplasm Proteins
PubMed: 38907278
DOI: 10.1186/s13048-024-01458-5