Lab Chip. 2023 Jul 11. doi: 10.1039/d3lc00147d. Online ahead of print.

ABSTRACT

In vitro investigation of a glomerular filtration barrier (GFB) remains difficult because of the inability to mimic its specialized structure, although various kidney diseases are characterized by GFB dysfunction. Here, the development of a microfluidic model that replicates the physiology of the GFB has been achieved by tunable glomerular basement membrane (gBM) deposition and 3D co-culture of podocytes with glomerular endothelial cells (gECs). By precisely controlling the thickness of the gBM, our model successfully reproduced the biphasic response of the GFB, where variations in gBM thickness influence barrier properties. Moreover, this microscale proximity of gECs and podocytes facilitated their dynamic crosstalk, which is essential for maintaining the integrity and function of the GFB. We observed that addition of gBM and podocytes enhanced barrier function of gECs by inducing up-regulation of gEC's tight junctions synergistically, and moreover, found an ultrastructure of gECs-gBM-podocytes' foot process contacting each other by confocal and TEM imaging. The dynamic interaction of gECs and podocytes played a significant role in the response to drug-induced injury and the regulation of barrier properties. Nephrotoxic injury simulated in our model helped to elucidate that the over-production of vascular endothelial growth factor A from the injured podocytes mediates GFB impairment. We believe that our GFB model can provide a valuable tool for mechanistic studies such as investigating GFB biology, comprehending disease mechanisms, and evaluating potential therapeutic approaches in a controlled and physiologically relevant environment.

PMID:37432664 | DOI:10.1039/d3lc00147d

G3 (Bethesda). 2023 Jul 11:jkad153. doi: 10.1093/g3journal/jkad153. Online ahead of print.

ABSTRACT

Subtelomeric gene silencing is the negative transcriptional regulation of genes located close to telomeres. This phenomenon occurs in a variety of eukaryotes with salient physiological implications, such as cell adherence, virulence, immune-system escape, and aging. The process has been widely studied in the budding yeast Saccharomyces cerevisiae, where genes involved in this process have been identified mostly on a gene-by-gene basis. Here, we introduce a quantitative approach to study gene silencing, that couples the classical URA3 reporter with GFP monitoring, amenable to high-throughput flow cytometry analysis. This dual silencing reporter was integrated into several subtelomeric loci in the genome, where it showed a gradual range of silencing effects. By crossing strains with this dual reporter at the COS12 and YFR057W subtelomeric query loci with gene-deletion mutants, we carried out a large-scale forward screen for potential silencing factors. The approach was replicable and allowed accurate detection of expression changes. Results of our comprehensive screen suggest that the main players influencing subtelomeric silencing were previously known, but additional potential factors underlying chromatin conformation are involved. We validate and report the novel silencing factor LGE1, a protein with unknown molecular function required for histone H2B ubiquitination. Our strategy can be readily combined with other reporters and gene perturbation collections, making it a versatile tool to study gene silencing at a genome-wide scale.

PMID:37431950 | DOI:10.1093/g3journal/jkad153

Food Funct. 2023 Jul 11. doi: 10.1039/d3fo00818e. Online ahead of print.

ABSTRACT

Glucagon-like peptide 1 (GLP-1) is a multifaceted intestinal hormone with diverse physiological functions throughout the body. Previously, we demonstrated that the steviol glycoside rebaudioside A (rebA) from Stevia rebaudiana stimulates the release of GLP-1 from mouse intestinal organoids and pig intestinal segments. To further unravel the underlying mechanisms, we examined the involvement of sweet- and bitter taste receptors and their associated signal transduction pathways. Experiments with mouse and human intestinal enteroendocrine cell lines (STC-1 and HuTu-80, respectively) confirmed that rebA stimulates GLP-1 release in a concentration-dependent manner. Experiments with selective inhibitors of sweet signalling in both the murine as well as the human enteroendocrine cells showed that the GLP-1-induced release by rebA occurs independently of the sweet taste receptor. Functional screening of 34 murine bitter taste receptors (Tas2rs) revealed an activation response with Tas2r108, Tas2r123 and Tas2r134. Moreover, we found evidence in human HuTu-80 cells, that TAS2R4 and TRPM5 are involved in rebA-induced GLP-1 secretion, suggesting a role for bitter taste signaling in gut hormone release. Interestingly, the rebA-dependent GLP-1 release may be modulated by GABA and 6-methoxyflavanone present in the diet. Together, our findings warrant further characterization of the specific metabolic effects of rebA among the non-caloric sweeteners.

PMID:37431625 | DOI:10.1039/d3fo00818e

Biol Sex Differ. 2023 Jul 10;14(1):45. doi: 10.1186/s13293-023-00531-w.

ABSTRACT

BACKGROUND: Physical weakness is a key component of frailty, and is highly prevalent in older adults. While females have a higher prevalence and earlier onset, sex differences in the development of frailty-related physical weakness are hardly studied. Therefore, we investigated the intramuscular changes that differentiate between fit and weak older adults for each sex separately.

METHODS: Male (n = 28) and female (n = 26) older adults (75 + years) were grouped on the basis of their ranks according to three frailty-related physical performance criteria. Muscle biopsies taken from vastus lateralis muscle were used for transcriptome and histological examination. Pairwise comparisons were made between the fittest and weakest groups for each sex separately, and potential sex-specific effects were assessed.

RESULTS: Weak females were characterized by a higher expression of inflammatory pathways and infiltration of NOX2-expressing immune cells, concomitant with a higher VCAM1 expression. Weak males were characterized by a smaller diameter of type 2 (fast) myofibers and lower expression of PRKN. In addition, weakness-associated transcriptome changes in the muscle were distinct from aging, suggesting that the pathophysiology of frailty-associated physical weakness does not necessarily depend on aging.

CONCLUSIONS: We conclude that physical weakness-associated changes in muscle are sex-specific and recommend that sex differences are taken into account in research on frailty, as these differences may have a large impact on the development of (pharmaceutical) interventions against frailty.

TRIAL REGISTRATION NUMBER: The FITAAL study was registered in the Dutch Trial Register, with registration code NTR6124 on 14-11-2016 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6124 ).

HIGHLIGHTS: • In female, but not male older adults, physical weakness was associated with a higher expression of intramuscular markers for inflammation. • In male, but not female older adults, physical weakness was associated with a smaller diameter of type 2 (fast) myofibers and lower PRKN expression. • Fit older adults (of both sexes) maintained expression levels comparable to young participants of weakness related genes, differing from frail participants.

PMID:37430322 | DOI:10.1186/s13293-023-00531-w

Nat Biomed Eng. 2023 Jul 10. doi: 10.1038/s41551-023-01058-6. Online ahead of print.

ABSTRACT

Engineering cells for adoptive therapy requires overcoming limitations in cell viability and, in the efficiency of transgene delivery, the duration of transgene expression and the stability of genomic integration. Here we report a gene-delivery system consisting of a Sleeping Beauty (SB) transposase encoded into a messenger RNA delivered by an adeno-associated virus (AAV) encoding an SB transposon that includes the desired transgene, for mediating the permanent integration of the transgene. Compared with lentiviral vectors and with the electroporation of plasmids of transposon DNA or minicircle DNA, the gene-delivery system, which we named MAJESTIC (for 'mRNA AAV-SB joint engineering of stable therapeutic immune cells'), offers prolonged transgene expression, as well as higher transgene expression, therapeutic-cell yield and cell viability. MAJESTIC can deliver chimeric antigen receptors (CARs) into T cells (which we show lead to strong anti-tumour activity in vivo) and also transduce natural killer cells, myeloid cells and induced pluripotent stem cells with bi-specific CARs, kill-switch CARs and synthetic T-cell receptors.

PMID:37430157 | DOI:10.1038/s41551-023-01058-6

Nat Methods. 2023 Jul;20(7):1104-1113. doi: 10.1038/s41592-023-01913-z. Epub 2023 Jul 6.

ABSTRACT

Genetically encoded voltage indicators (GEVIs) enable optical recording of electrical signals in the brain, providing subthreshold sensitivity and temporal resolution not possible with calcium indicators. However, one- and two-photon voltage imaging over prolonged periods with the same GEVI has not yet been demonstrated. Here, we report engineering of ASAP family GEVIs to enhance photostability by inversion of the fluorescence-voltage relationship. Two of the resulting GEVIs, ASAP4b and ASAP4e, respond to 100-mV depolarizations with ≥180% fluorescence increases, compared with the 50% fluorescence decrease of the parental ASAP3. With standard microscopy equipment, ASAP4e enables single-trial detection of spikes in mice over the course of minutes. Unlike GEVIs previously used for one-photon voltage recordings, ASAP4b and ASAP4e also perform well under two-photon illumination. By imaging voltage and calcium simultaneously, we show that ASAP4b and ASAP4e can identify place cells and detect voltage spikes with better temporal resolution than commonly used calcium indicators. Thus, ASAP4b and ASAP4e extend the capabilities of voltage imaging to standard one- and two-photon microscopes while improving the duration of voltage recordings.

PMID:37429962 | DOI:10.1038/s41592-023-01913-z

Nat Aging. 2023 Jul 10. doi: 10.1038/s43587-023-00453-7. Online ahead of print.

ABSTRACT

Aging is accompanied by homeostatic and functional dysregulation of multiple immune cell subsets. Group 3 innate lymphoid cells (ILC3s) constitute a heterogeneous cell population that plays pivotal roles in intestinal immunity. In this study, we found that ILC3s in aged mice exhibited dysregulated homeostasis and function, leading to bacterial and fungal infection susceptibility. Moreover, our data revealed that the enrichment of the H3K4me3 modification in effector genes of aged gut CCR6+ ILC3s was specifically decreased compared to young mice counterparts. Disruption of Cxxc finger protein 1 (Cxxc1) activity, a key subunit of H3K4 methyltransferase, in ILC3s led to similar aging-related phenotypes. An integrated analysis revealed Kruppel-like factor 4 (Klf4) as a potential Cxxc1 target. Klf4 overexpression partially restored the differentiation and functional defects seen in both aged and Cxxc1-deficient intestinal CCR6+ ILC3s. Therefore, these data suggest that targeting intestinal ILC3s may provide strategies to protect against age-related infections.

PMID:37429951 | DOI:10.1038/s43587-023-00453-7

Plant Physiol. 2023 Jul 11:kiad401. doi: 10.1093/plphys/kiad401. Online ahead of print.

ABSTRACT

The molecular innovation underpinning efficient carbon and energy metabolism during evolution of land plants remains largely unknown. Invertase-mediated sucrose cleavage into hexoses is central to fuel growth. Why some cytoplasmic invertases (CINs) function in the cytosol, whereas others operate in chloroplasts and mitochondria, is puzzling. We attempted to shed light on this question from an evolutionary perspective. Our analyses indicated that plant CINs originated from an putatively orthologous ancestral gene in cyanobacteria and formed the plastidic CIN (α1 clade) through endo-symbiotic gene transfer, while its duplication in algae with a loss of its signal peptide produced the β clade CINs in the cytosol. The mitochondrial CINs (α2) derived from duplication of the plastidic CINs and co-evolved with vascular plants. Importantly, the copy number of mitochondrial and plastidic CINs increased upon the emergence of seed plants, corresponding with the rise of respiratory, photosynthetic and growth rates. The cytosolic CIN (β subfamily) kept expanding from algae to gymnosperm, indicating its role in supporting the increase in carbon use efficiency during evolution. Affinity purification mass spectrometry identified a cohort of proteins interacting with α1 and 2 CINs, which points to their roles in plastid and mitochondrial glycolysis, oxidative stress tolerance and the maintenance of subcellular sugar homeostasis. Collectively, the findings indicate evolutionary roles of α1 and α2 CINs in chloroplasts and mitochondria for achieving high photosynthetic and respiratory rates, respectively, which, together with the expanding of cytosolic CINs, likely underpin the colonization of land plants through fueling rapid growth and biomass production.

PMID:37429000 | DOI:10.1093/plphys/kiad401

PLoS Comput Biol. 2023 Jul 10;19(7):e1011289. doi: 10.1371/journal.pcbi.1011289. Online ahead of print.

ABSTRACT

Stochastic models of sequential mutation acquisition are widely used to quantify cancer and bacterial evolution. Across manifold scenarios, recurrent research questions are: how many cells are there with n alterations, and how long will it take for these cells to appear. For exponentially growing populations, these questions have been tackled only in special cases so far. Here, within a multitype branching process framework, we consider a general mutational path where mutations may be advantageous, neutral or deleterious. In the biologically relevant limiting regimes of large times and small mutation rates, we derive probability distributions for the number, and arrival time, of cells with n mutations. Surprisingly, the two quantities respectively follow Mittag-Leffler and logistic distributions regardless of n or the mutations' selective effects. Our results provide a rapid method to assess how altering the fundamental division, death, and mutation rates impacts the arrival time, and number, of mutant cells. We highlight consequences for mutation rate inference in fluctuation assays.

PMID:37428805 | DOI:10.1371/journal.pcbi.1011289

J Physiol. 2023 Jul 10. doi: 10.1113/JP284994. Online ahead of print.

ABSTRACT

Calmodulin (CaM) is a highly conserved mediator of calcium (Ca2+ )-dependent signalling and modulates various cardiac ion channels. Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS). LQTS patients display prolonged ventricular recovery times (QT interval), increasing their risk of incurring life-threatening arrhythmic events. Loss-of-function mutations to Kv7.1 (which drives the slow delayed rectifier potassium current, IKs, a key ventricular repolarising current) are the largest contributor to congenital LQTS (>50% of cases). CaM modulates Kv7.1 to produce a Ca2+ -sensitive IKs, but little is known about the consequences of LQTS-associated CaM mutations on Kv7.1 function. Here, we present novel data characterising the biophysical and modulatory properties of three LQTS-associated CaM variants (D95V, N97I and D131H). We showed that mutations induced structural alterations in CaM and reduced affinity for Kv7.1, when compared with wild-type (WT). Using HEK293T cells expressing Kv7.1 channel subunits (KCNQ1/KCNE1) and patch-clamp electrophysiology, we demonstrated that LQTS-associated CaM variants reduced current density at systolic Ca2+ concentrations (1 μm), revealing a direct QT-prolonging modulatory effect. Our data highlight for the first time that LQTS-associated perturbations to CaM's structure impede complex formation with Kv7.1 and subsequently result in reduced IKs. This provides a novel mechanistic insight into how the perturbed structure-function relationship of CaM variants contributes to the LQTS phenotype. KEY POINTS: Calmodulin (CaM) is a ubiquitous, highly conserved calcium (Ca2+ ) sensor playing a key role in cardiac muscle contraction. Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS), a life-threatening cardiac arrhythmia syndrome. LQTS-associated CaM variants (D95V, N97I and D131H) induced structural alterations, altered binding to Kv7.1 and reduced IKs. Our data provide a novel mechanistic insight into how the perturbed structure-function relationship of CaM variants contributes to the LQTS phenotype.

PMID:37428651 | DOI:10.1113/JP284994

Methods Mol Biol. 2023;2680:231-244. doi: 10.1007/978-1-0716-3275-8_14.

ABSTRACT

This protocol is focused on using the recently established planarian infection model system to study host-pathogen interactions during fungal infection. Here, we describe in detail the infection of the planarian Schmidtea mediterranea with the human fungal pathogen Candida albicans. This simple and reproducible model system allows for rapid visualization of tissue damage throughout different infection timepoints. We note that this model system has been optimized for use with C. albicans, but should also be applicable for use with other pathogens of interest.

PMID:37428381 | DOI:10.1007/978-1-0716-3275-8_14

Elife. 2023 Jul 10;12:e83891. doi: 10.7554/eLife.83891. Online ahead of print.

ABSTRACT

Reinforcement learning research in humans and other species indicates that rewards are represented in a context-dependent manner. More specifically, reward representations seem to be normalized as a function of the value of the alternative options. The dominant view postulates that value context-dependence is achieved via a divisive normalization rule, inspired by perceptual decision-making research. However, behavioral and neural evidence points to another plausible mechanism: range normalization. Critically, previous experimental designs were ill-suited to disentangle the divisive and the range normalization accounts, which generate similar behavioral predictions in many circumstances. To address this question, we designed a new learning task where we manipulated, across learning contexts, the number of options and the value ranges. Behavioral and computational analyses falsify the divisive normalization account and rather provide support for the range normalization rule. Together, these results shed new light on the computational mechanisms underlying context-dependence in learning and decision-making.

PMID:37428155 | DOI:10.7554/eLife.83891

Elife. 2023 Jul 10;12:e87181. doi: 10.7554/eLife.87181.

ABSTRACT

Actin dynamics in cell motility, division, and phagocytosis is regulated by complex factors with multiple feedback loops, often leading to emergent dynamic patterns in the form of propagating waves of actin polymerization activity that are poorly understood. Many in the actin wave community have attempted to discern the underlying mechanisms using experiments and/or mathematical models and theory. Here, we survey methods and hypotheses for actin waves based on signaling networks, mechano-chemical effects, and transport characteristics, with examples drawn from Dictyostelium discoideum, human neutrophils, Caenorhabditis elegans, and Xenopus laevis oocytes. While experimentalists focus on the details of molecular components, theorists pose a central question of universality: Are there generic, model-independent, underlying principles, or just boundless cell-specific details? We argue that mathematical methods are equally important for understanding the emergence, evolution, and persistence of actin waves and conclude with a few challenges for future studies.

PMID:37428017 | DOI:10.7554/eLife.87181

Elife. 2023 Jul 10;12:e82597. doi: 10.7554/eLife.82597.

ABSTRACT

Hypoxia requires metabolic adaptations to sustain energetically demanding cellular activities. While the metabolic consequences of hypoxia have been studied extensively in cancer cell models, comparatively little is known about how primary cell metabolism responds to hypoxia. Thus, we developed metabolic flux models for human lung fibroblast and pulmonary artery smooth muscle cells proliferating in hypoxia. Unexpectedly, we found that hypoxia decreased glycolysis despite activation of hypoxia-inducible factor 1α (HIF-1α) and increased glycolytic enzyme expression. While HIF-1α activation in normoxia by prolyl hydroxylase (PHD) inhibition did increase glycolysis, hypoxia blocked this effect. Multi-omic profiling revealed distinct molecular responses to hypoxia and PHD inhibition, and suggested a critical role for MYC in modulating HIF-1α responses to hypoxia. Consistent with this hypothesis, MYC knockdown in hypoxia increased glycolysis and MYC over-expression in normoxia decreased glycolysis stimulated by PHD inhibition. These data suggest that MYC signaling in hypoxia uncouples an increase in HIF-dependent glycolytic gene transcription from glycolytic flux.

PMID:37428010 | DOI:10.7554/eLife.82597

J Vis Exp. 2023 Jun 23;(196). doi: 10.3791/65281.

ABSTRACT

The optokinetic reflex (OKR) is an essential innate eye movement that is triggered by the global motion of the visual environment and serves to stabilize retinal images. Due to its importance and robustness, the OKR has been used to study visual-motor learning and to evaluate the visual functions of mice with different genetic backgrounds, ages, and drug treatments. Here, we introduce a procedure for evaluating OKR responses of head-fixed mice with high accuracy. Head fixation can rule out the contribution of vestibular stimulation on eye movements, making it possible to measure eye movements triggered only by visual motion. The OKR is elicited by a virtual drum system, in which a vertical grating presented on three computer monitors drifts horizontally in an oscillatory manner or unidirectionally at a constant velocity. With this virtual reality system, we can systematically change visual parameters like spatial frequency, temporal/oscillation frequency, contrast, luminance, and the direction of gratings, and quantify tuning curves of visual feature selectivity. High-speed infrared video-oculography ensures accurate measurement of the trajectory of eye movements. The eyes of individual mice are calibrated to provide opportunities to compare the OKRs between animals of different ages, genders, and genetic backgrounds. The quantitative power of this technique allows it to detect changes in the OKR when this behavior plastically adapts due to aging, sensory experience, or motor learning; thus, it makes this technique a valuable addition to the repertoire of tools used to investigate the plasticity of ocular behaviors.

PMID:37427914 | DOI:10.3791/65281

Gut Microbes. 2023 Jan-Dec;15(1):2233689. doi: 10.1080/19490976.2023.2233689.

ABSTRACT

Colibactin, a bacterial genotoxin produced by E. coli strains harboring the pks genomic island, induces cytopathic effects, such as DNA breaks, cell cycle arrest, and apoptosis. Patients with inflammatory bowel diseases, such as ulcerative colitis, display changes in their microbiota with the expansion of E. coli. Whether and how colibactin affects the integrity of the colonic mucosa and whether pks+ E. coli contributes to the pathogenesis of colitis is not clear. Using a gnotobiotic mouse model, we show that under homeostatic conditions, pks+ E. coli do not directly interact with the epithelium or affect colonic integrity. However, upon short-term chemical disruption of mucosal integrity, pks+ E. coli gain direct access to the epithelium, causing epithelial injury and chronic colitis, while mice colonized with an isogenic ΔclbR mutant incapable of producing colibactin show a rapid recovery. pks+ E. coli colonized mice are unable to reestablish a functional barrier. In turn, pks+ E. coli remains in direct contact with the epithelium, perpetuating the process and triggering chronic mucosal inflammation that morphologically and transcriptionally resembles human ulcerative colitis. This state is characterized by impaired epithelial differentiation and high proliferative activity, which is associated with high levels of stromal R-spondin 3. Genetic overexpression of R-spondin 3 in colon myofibroblasts is sufficient to mimic barrier disruption and expansion of E. coli. Together, our data reveal that pks+ E. coli are pathobionts that promote severe injury and initiate a proinflammatory trajectory upon contact with the colonic epithelium, resulting in a chronic impairment of tissue integrity.

PMID:37427832 | DOI:10.1080/19490976.2023.2233689

Plant Physiol. 2023 Jul 10:kiad403. doi: 10.1093/plphys/kiad403. Online ahead of print.

ABSTRACT

Regulation of intracellular sugar homeostasis is maintained by regulation of activities of sugar import and export proteins residing at the tonoplast. We show here that the EARLY RESPONSE TO DEHYDRATION6-LIKE4 (ERDL4) protein, a member of the monosaccharide transporter family, resides in the vacuolar membrane in Arabidopsis (Arabidopsis thaliana). Gene expression and subcellular fractionation studies indicated that ERDL4 participates in fructose allocation across the tonoplast. Overexpression of ERDL4 increased total sugar levels in leaves due to a concomitantly induced stimulation of TONOPLAST SUGAR TRANSPORTER 2 (TST2) expression, coding for the major vacuolar sugar loader. This conclusion is supported by the finding that tst1-2 knockout lines overexpressing ERDL4 lack increased cellular sugar levels. ERDL4 activity contributing to the coordination of cellular sugar homeostasis is also indicated by two further observations. Firstly, ERDL4 and TST genes exhibit an opposite regulation during a diurnal rhythm, and secondly, the ERDL4 gene is markedly expressed during cold acclimation, representing a situation in which TST activity needs to be upregulated. Moreover, ERDL4-overexpressing plants show larger rosettes and roots, a delayed flowering time, and increased total seed yield. Consistently, erdl4 knockout plants show impaired cold acclimation and freezing tolerance along with reduced plant biomass. In summary, we show that modification of cytosolic fructose levels influences plant organ development and stress tolerance.

PMID:37427783 | DOI:10.1093/plphys/kiad403

Front Cell Dev Biol. 2023 Jun 22;11:1197204. doi: 10.3389/fcell.2023.1197204. eCollection 2023.

ABSTRACT

Adverse Outcome Pathways (AOPs) are useful tools for assessing the potential risks associated with exposure to various stressors, including chemicals and environmental contaminants. They provide a framework for understanding the causal relationships between different biological events that can lead to adverse outcomes (AO). However, developing an AOP is a challenging task, particularly in identifying the molecular initiating events (MIEs) and key events (KEs) that constitute it. Here, we propose a systems biology strategy that can assist in the development of AOPs by screening publicly available databases, literature with the text mining tool AOP-helpFinder, and pathway/network analyses. This approach is straightforward to use, requiring only the name of the stressor and adverse outcome to be studied. From this, it quickly identifies potential KEs and literature providing mechanistic information on the links between the KEs. The proposed approach was applied to the recently developed AOP 441 on radiation-induced microcephaly, resulting in the confirmation of the KEs that were already present and identification of new relevant KEs, thereby validating the strategy. In conclusion, our systems biology approach represents a valuable tool to simplify the development and enrichment of Adverse Outcome Pathways (AOPs), thus supporting alternative methods in toxicology.

PMID:37427375 | PMC:PMC10323360 | DOI:10.3389/fcell.2023.1197204

Transl Pediatr. 2023 Jun 30;12(6):1213-1224. doi: 10.21037/tp-23-133. Epub 2023 Jun 19.

ABSTRACT

BACKGROUND AND OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common morbidity associated with prematurity and remains a significant clinical challenge. Bioinformatic approaches, such as genomics, transcriptomics, and proteomics, have emerged as novel methods for studying the underlying mechanisms driving BPD pathogenesis. These methods can be used alongside clinical data to develop a better understanding of BPD and potentially identify the most at risk neonates within the first few weeks of neonatal life. The objective of this review is to provide an overview of the current state-of-the-art in bioinformatics for BPD research.

METHODS: We conducted a literature review of bioinformatics approaches for BPD using PubMed. The following keywords were used: "biomedical informatics", "bioinformatics", "bronchopulmonary dysplasia", and "omics".

KEY CONTENT AND FINDINGS: This review highlighted the importance of omic-approaches to better understand BPD and potential avenues for future research. We described the use of machine learning (ML) and the need for systems biology methods for integrating large-scale data from multiple tissues. We summarized a handful of studies that utilized bioinformatics for BPD in order to better provide a view of where things currently stand, identify areas of ongoing research, and concluded with challenges that remain in the field.

CONCLUSIONS: Bioinformatics has the potential to enable a more comprehensive understanding of BPD pathogenesis, facilitating a personalized and precise approach to neonatal care. As we continue to push the boundaries of biomedical research, biomedical informatics (BMI) will undoubtedly play a key role in unraveling new frontiers in disease understanding, prevention, and treatment.

PMID:37427053 | PMC:PMC10326754 | DOI:10.21037/tp-23-133

Front Plant Sci. 2023 Jun 22;14:1227279. doi: 10.3389/fpls.2023.1227279. eCollection 2023.

NO ABSTRACT

PMID:37426990 | PMC:PMC10324574 | DOI:10.3389/fpls.2023.1227279