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Journal of Experimental Botany Jul 2023Plant morphology and anatomy strongly influence agricultural yield. Crop domestication has strived for desirable growth and developmental traits, such as larger and more... (Review)
Review
Plant morphology and anatomy strongly influence agricultural yield. Crop domestication has strived for desirable growth and developmental traits, such as larger and more fruits and semi-dwarf architecture. Genetic engineering has accelerated rational, purpose-driven engineering of plant development, but it can be unpredictable. Developmental pathways are complex and riddled with environmental and hormonal inputs, as well as feedback and feedforward interactions, which occur at specific times and places in a growing multicellular organism. Rational modification of plant development would probably benefit from precision engineering based on synthetic biology approaches. This review outlines recently developed synthetic biology technologies for plant systems and highlights their potential for engineering plant growth and development. Streamlined and high-capacity genetic construction methods (Golden Gate DNA Assembly frameworks and toolkits) allow fast and variation-series cloning of multigene transgene constructs. This, together with a suite of gene regulation tools (e.g. cell type-specific promoters, logic gates, and multiplex regulation systems), is starting to enable developmental pathway engineering with predictable outcomes in model plant and crop species.
Topics: Synthetic Biology; Genetic Engineering; Plants; DNA; Developmental Biology; Cloning, Molecular
PubMed: 37155965
DOI: 10.1093/jxb/erad169 -
Biological Reviews of the Cambridge... Aug 2023The characteristic maximum lifespan varies enormously across animal species from a few hours to hundreds of years. This argues that maximum lifespan, and the ageing...
The characteristic maximum lifespan varies enormously across animal species from a few hours to hundreds of years. This argues that maximum lifespan, and the ageing process that itself dictates lifespan, are to a large extent genetically determined. Although controversial, this is supported by firm evidence that semelparous species display evolutionarily programmed ageing in response to reproductive and environmental cues. Parabiosis experiments reveal that ageing is orchestrated systemically through the circulation, accompanied by programmed changes in hormone levels across a lifetime. This implies that, like the circadian and circannual clocks, there is a master 'clock of age' (circavital clock) located in the limbic brain of mammals that modulates systemic changes in growth factor and hormone secretion over the lifespan, as well as systemic alterations in gene expression as revealed by genomic methylation analysis. Studies on accelerated ageing in mice, as well as human longevity genes, converge on evolutionarily conserved fibroblast growth factors (FGFs) and their receptors, including KLOTHO, as well as insulin-like growth factors (IGFs) and steroid hormones, as key players mediating the systemic effects of ageing. Age-related changes in these and multiple other factors are inferred to cause a progressive decline in tissue maintenance through failure of stem cell replenishment. This most severely affects the immune system, which requires constant renewal from bone marrow stem cells. Age-related immune decline increases risk of infection whereas lifespan can be extended in germfree animals. This and other evidence suggests that infection is the major cause of death in higher organisms. Immune decline is also associated with age-related diseases. Taking the example of Alzheimer's disease (AD), we assess the evidence that AD is caused by immunosenescence and infection. The signature protein of AD brain, Aβ, is now known to be an antimicrobial peptide, and Aβ deposits in AD brain may be a response to infection rather than a cause of disease. Because some cognitively normal elderly individuals show extensive neuropathology, we argue that the location of the pathology is crucial - specifically, lesions to limbic brain are likely to accentuate immunosenescence, and could thus underlie a vicious cycle of accelerated immune decline and microbial proliferation that culminates in AD. This general model may extend to other age-related diseases, and we propose a general paradigm of organismal senescence in which declining stem cell proliferation leads to programmed immunosenescence and mortality.
Topics: Animals; Humans; Mice; Aged; Immunosenescence; Alzheimer Disease; Cell Self Renewal; Aging; Mammals; Hormones
PubMed: 37068798
DOI: 10.1111/brv.12959 -
Biomedicine & Pharmacotherapy =... Nov 2023Diabetic foot ulcers, a common complication of diabetes mellitus, significantly impact patients' quality of life and impose a substantial economic burden on healthcare...
Diabetic foot ulcers, a common complication of diabetes mellitus, significantly impact patients' quality of life and impose a substantial economic burden on healthcare systems. However, the currently used treatments are associated with various challenges and the traditionally used dressings lack functional efficacy. Oxidative stress is believed to play a vital role in diabetic wound healing. Therefore, nicotinamide mononucleotide (NMN), which is known for its antioxidant properties, offers the potential to accelerate the wound-healing process. Here, a thermosensitive composite hydrogel was synthesized by mixing Pluronic F127 and Pluronic F68 with an antibacterial component chitosan. The hydrogel exhibited favorable properties including a stable structure, appropriate solid-liquid phase change, loose porosity, slow-release, antibacterial properties, and biocompatibility. In vitro experiments demonstrated that the NMN-loaded temperature-sensitive hydrogel effectively promoted cell proliferation, migration, and angiogenesis and exhibited antioxidant activity. In diabetic thickness skin defect models, NMN-loaded temperature-sensitive hydrogel treatment significantly accelerated wound healing by promoting collagen synthesis, angiogenesis, and increased expression of vascular endothelial growth factor and transforming growth factor- β1. In summary, NMN-loaded temperature-sensitive hydrogel can promote diabetic wound healing in a simple, economical, effective, and safe manner, with potential application in treating diabetic wounds.
PubMed: 37688988
DOI: 10.1016/j.biopha.2023.115431 -
American Journal of Obstetrics &... Aug 2023Antenatal detection of accelerated fetal growth and macrosomia in pregnancies complicated by diabetes mellitus is important for patient counseling and management....
BACKGROUND
Antenatal detection of accelerated fetal growth and macrosomia in pregnancies complicated by diabetes mellitus is important for patient counseling and management. Sonographic fetal weight estimation is the most commonly used tool to predict birthweight and macrosomia. However, the predictive accuracy of sonographic fetal weight estimation for these outcomes is limited. In addition, an up-to-date sonographic fetal weight estimation is often unavailable before birth. This may result in a failure to identify macrosomia, especially in pregnancies complicated by diabetes mellitus where care providers might underestimate fetal growth rate. Therefore, there is a need for better tools to detect and alert care providers to the potential risk of accelerated fetal growth and macrosomia.
OBJECTIVE
This study aimed to develop and validate prediction models for birthweight and macrosomia in pregnancies complicated by diabetes mellitus.
STUDY DESIGN
This was a completed retrospective cohort study of all patients with a singleton live birth at ≥36 weeks of gestation complicated by preexisting or gestational diabetes mellitus observed at a single tertiary center between January 2011 and May 2022. Candidate predictors included maternal age, parity, type of diabetes mellitus, information from the most recent sonographic fetal weight estimation (including estimated fetal weight, abdominal circumference z score, head circumference-to-abdomen circumference z score ratio, and amniotic fluid), fetal sex, and the interval between ultrasound examination and birth. The study outcomes were macrosomia (defined as birthweights >4000 and >4500 g), large for gestational age (defined as a birthweight >90th percentile for gestational age), and birthweight (in grams). Multivariable logistic regression models were used to estimate the probability of dichotomous outcomes, and multivariable linear regression models were used to estimate birthweight. Model discrimination and predictive accuracy were calculated. Internal validation was performed using the bootstrap resampling technique.
RESULTS
A total of 2465 patients met the study criteria. Most patients had gestational diabetes mellitus (90%), 6% of patients had type 2 diabetes mellitus, and 4% of patients had type 1 diabetes mellitus. The overall proportions of infants with birthweights >4000 g, >4500 g, and >90th percentile for gestational age were 8%, 1%, and 12%, respectively. The most contributory predictor variables were estimated fetal weight, abdominal circumference z score, ultrasound examination to birth interval, and type of diabetes mellitus. The models for the 3 dichotomous outcomes had high discriminative accuracy (area under the curve receiver operating characteristic curve, 0.929-0.979), which was higher than that achieved with estimated fetal weight alone (area under the curve receiver operating characteristic curve, 0.880-0.931). The predictive accuracy of the models had high sensitivity (87%-100%), specificity (84%-92%), and negative predictive values (84%-92%). The predictive accuracy of the model for birthweight had low systematic and random errors (0.6% and 7.5%, respectively), which were considerably smaller than the corresponding errors achieved with estimated fetal weight alone (-5.9% and 10.8%, respectively). The proportions of estimates within 5%, 10%, and 15% of the actual birthweight were high (52.3%, 82.9%, and 94.9%, respectively).
CONCLUSION
The prediction models developed in the current study were associated with greater predictive accuracy for macrosomia, large for gestational age, and birthweight than the current standard of care that includes estimated fetal weight alone. These models may assist care providers in counseling patients regarding the optimal timing and mode of delivery.
Topics: Humans; Pregnancy; Female; Birth Weight; Fetal Macrosomia; Diabetes, Gestational; Fetal Weight; Retrospective Studies; Diabetes Mellitus, Type 2; Ultrasonography, Prenatal; Parity
PubMed: 37286100
DOI: 10.1016/j.ajogmf.2023.101042 -
Cell Death & Disease Aug 2023Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) has been reported to play an oncogenic role in several cancers. However, the biological...
Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) has been reported to play an oncogenic role in several cancers. However, the biological functions and regulatory mechanism of NUCKS1 in osteosarcoma have not been fully understood. In this study, we reported that NUCKS1 was significantly increased in osteosarcoma. Depletion of NUCKS1 decreased osteosarcoma cell proliferation and metastasis in vivo and in vitro. Overexpression of NUCKS1 accelerated osteosarcoma cell aggressiveness. Mechanistically, NUCKS1 facilitated asparagine (Asn) synthesis by transcriptionally upregulating asparagine synthetase (ASNS) expression and elevating the levels of Asn in osteosarcoma cells, leading to increased cell growth and metastasis. Inhibition of ASNS or reduction of Asn decreased osteosarcoma cell aggressiveness and impaired the promoting effects of NUCKS1 on tumorigenesis and metastasis. Furthermore, we also found that by acting as a sponge for miR-4768-3p, LINC00629 promoted NUCKS1 expression. Collectively, our findings highlight the role of NUCKS1 in regulating asparagine metabolism and reveal that LINC00629 is an important regulator of NUCKS1 that contributes to NUCKS1 upregulation in osteosarcoma.
Topics: Humans; Cell Line, Tumor; Asparagine; Gene Expression Regulation, Neoplastic; Up-Regulation; Osteosarcoma; Cell Proliferation; MicroRNAs; Bone Neoplasms
PubMed: 37528150
DOI: 10.1038/s41419-023-06010-9 -
International Journal of Molecular... Jul 2023The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured (BFNB) on the promotion of...
The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured (BFNB) on the promotion of hair growth in C57BL/6 mice. The characterization of the follicular phases and histomorphological analysis showed that the topical application of the formulation for 15 days significantly increased pigmentation and hair growth on the dorsum and head of the mice. Additionally, an acceleration of the follicular cycle phases was observed, along with an increase in the number of follicles, hair length, and diameter, compared to mice treated with minoxidil. In silico analysis and molecular characterization demonstrated that BFNB enhances the expression of epidermal growth factor (EGF) and fibroblast growth factor 7 (FGF7), activating the PI3K-AKT-β-catenin signaling pathway, as well as the expression of PCNA, KI-67, Cyclin D1, and Cyclin E, regulating the cell cycle and cell proliferation, crucial events for hair regeneration. Our results strongly suggest the utility of BFNB as a therapeutic alternative to stimulate hair growth and promote hair health.
Topics: Animals; Mice; beta Catenin; Catenins; Cell Proliferation; Epidermal Growth Factor; Fibroblast Growth Factor 7; Hair; Hair Follicle; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
PubMed: 37569486
DOI: 10.3390/ijms241512110 -
The Science of the Total Environment Nov 2023Plants exposed to a variety of abiotic and biotic stressors including environmental pollution and global warming pose significant threats to biodiversity and ecosystem... (Review)
Review
Plants exposed to a variety of abiotic and biotic stressors including environmental pollution and global warming pose significant threats to biodiversity and ecosystem services. Despite substantial literature documenting how plants adapt to distinct stressors, there still is a lack of knowledge regarding responses to multiple stressors and how these affects growth and development. Exposure of plants to concurrent biotic and abiotic stressors such as cadmium and drought, leads to pronounced inhibition in above ground biomass, imbalance in oxidative homeostasis, nutrient assimilation and stunted root growth, elucidating the synergistic interactions of multiple stressors culminating in adverse physiological outcomes. Impact of elevated heavy metal and water deficit exposure extends beyond growth and development, influencing the biodiversity of the microenvironment including the rhizosphere nutrient profile and microbiome. These findings have significant implications for plant-stress interactions and ecosystem functioning that prompt immediate action in order to eliminate effect of pollution and address global environmental issues to promote sustainable tolerance for multiple stress combinations in plants. Here, we review plant tolerance against stress combinations, highlighting the need for interdisciplinary approaches and advanced technologies, such as omics and molecular tools, to achieve a comprehensive understanding of underlying stress tolerance mechanisms. To accelerate progress towards developing stress-tolerance in plants against multiple environmental stressors, future research in plant stress tolerance should adopt a collaborative approach, involving researchers from multiple disciplines with diverse expertise and resources.
Topics: Ecosystem; Stress, Physiological; Plants; Rhizosphere; Biodiversity
PubMed: 37524179
DOI: 10.1016/j.scitotenv.2023.165832 -
Cytotherapy Nov 2023Extracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However,...
BACKGROUND AIMS
Extracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications.
METHODS
In this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle-incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field.
RESULTS
Following the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and β-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis.
CONCLUSIONS
The proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.
Topics: Mice; Animals; Hair Follicle; Skin; Mesenchymal Stem Cells; Cell Proliferation; Magnetic Phenomena
PubMed: 37516947
DOI: 10.1016/j.jcyt.2023.07.001 -
Placenta Sep 2023As presently conceptualised, the artificial placenta (AP) is an experimental life support platform for extremely preterm infants (i.e. 400-600 g; 21-23 weeks of... (Review)
Review
As presently conceptualised, the artificial placenta (AP) is an experimental life support platform for extremely preterm infants (i.e. 400-600 g; 21-23 weeks of gestation) born at the border of viability. It is based around the oxygenation of the periviable fetus using gas-exchangers connected to the fetal vasculature. In this system, the lung remains fluid-filled and the fetus remains in a quiescent state. The AP has been in development for some sixty years. Over this time, animal experimental models have evolved iteratively from employing external pump-driven systems used to support comparatively mature fetuses (generally goats or sheep) to platforms driven by the fetal heart and used successfully to maintain extremely premature fetuses weighing around 600 g. Simultaneously, sizable advances in neonatal and obstetric care mean that the nature of a potential candidate patient for this therapy, and thus the threshold success level for justifying its adoption, have both changed markedly since this approach was first conceived. Five landmark breakthroughs have occurred over the developmental history of the AP: i) the first human studies reported in the 1950's; ii) foundation animal studies reported in the 1960's; iii) the first extended use of AP technology combined with fetal pulmonary resuscitation reported in the 1990s; iv) the development of AP systems powered by the fetal heart reported in the 2000's; and v) the adaption of this technology to maintain extremely preterm fetuses (i.e. 500-600 g body weight) reported in the 2010's. Using this framework, the present paper will provide a review of the developmental history of this long-running experimental system and up-to-date assessment of the published field today. With the apparent acceleration of AP technology towards clinical application, there has been an increase in the attention paid to the field, along with some inaccurate commentary regarding its potential application and merits. Additionally, this paper will address several misrepresentations regarding the potential application of AP technology that serve to distract from the significant potential of this approach to greatly improve outcomes for extremely preterm infants born at or close to the present border of viability.
Topics: Infant, Newborn; Infant; Female; Pregnancy; Humans; Animals; Sheep; Fetal Heart; Prenatal Care; Body Weight; Goats; Infant, Extremely Premature; Perception
PubMed: 37743742
DOI: 10.1016/j.placenta.2022.10.003 -
American Journal of Epidemiology Aug 2023Early puberty onset is associated with higher risk of diabetes, but most studies have not accounted for childhood factors that may confound the association. Using data...
Early puberty onset is associated with higher risk of diabetes, but most studies have not accounted for childhood factors that may confound the association. Using data from a study conducted in an Indigenous community in Arizona (1965-2007), we examined associations of timing and velocity of the adolescent growth spurt with type 2 diabetes, and whether these associations are mediated by childhood body mass index and insulinemia. Adolescent growth parameters were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, for 861 participants with height measurements spanning the whole period of growth. In males, older age at take-off, age at peak velocity, and age at maturation were associated with decreased prevalence of diabetes (odds ratio (OR) = 0.43 per year, 95% confidence interval (CI): 0.27, 0.69; OR = 0.50, 95% CI: 0.35, 0.72; OR = 0.58, 95% CI: 0.41, 0.83, respectively), while higher velocity at take-off was associated with increased risk (OR = 3.47 per cm/year, 95% CI: 1.87, 6.42) adjusting for age, birth year, and maternal diabetes. Similar results were observed with incident diabetes. Our findings suggest that an early and accelerated adolescent growth spurt is a risk factor for diabetes, at least in males. These associations are only partially explained by measures of adiposity and insulinemia.
Topics: Adolescent; Female; Humans; Male; American Indian or Alaska Native; Body Height; Body Mass Index; Diabetes Mellitus, Type 2; Longitudinal Studies; Puberty; Risk Factors; Adolescent Development
PubMed: 37083933
DOI: 10.1093/aje/kwad100