-
Minerva Pediatrics Dec 2021Pediatric obesity is a growing and alarming global health problem and represents an important determinant of morbidity. Since nutrition plays an important role in... (Review)
Review
Pediatric obesity is a growing and alarming global health problem and represents an important determinant of morbidity. Since nutrition plays an important role in regulating growth and development, the excess weight gain related to overnutrition can affect growth patterns, bone maturation and pubertal development. The purpose of this review was to summarize the current knowledge about the effect of primary obesity on linear growth and pubertal development in children and adolescents. Evidence about regulatory hormones and adipokines that may be involved in the physiology of childhood growth in the context of obesity were also discussed. The most recent literature confirms previous studies indicating that linear growth is accelerated (mainly due to longer trunks rather than longer legs) and bone age is advanced in prepubertal children with obesity, while there is a reduction of pubertal height gain and attainment of normal adult height. Conflicting results are reported on the timing of puberty, specifically in boys. Indeed, previous studies suggested earlier onset of puberty in obese girls and overweight boys, and a delayed puberty in obese boys. Conversely, the most recent studies show more consistently an earlier onset and completion of pubertal development also in boys with obesity. Considering the false belief of health associated with transient taller stature in children and the adverse outcomes related to early puberty, interventions on diet and physical activity are urgently needed to tackle the epidemics of childhood obesity in public health and clinical setting.
Topics: Adolescent; Adult; Body Height; Body Weight; Child; Female; Humans; Male; Overweight; Pediatric Obesity; Puberty
PubMed: 34309346
DOI: 10.23736/S2724-5276.21.06543-5 -
Clinical Epigenetics Aug 2021In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life. (Comparative Study)
Comparative Study
BACKGROUND
In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life.
METHODS
Participants were from the Medical Research Council National Survey of Health and Development (n = 1376). Four DNAm age acceleration (AgeAccel) biomarkers were measured when participants were aged 53 years: AgeAccelHannum; AgeAccelHorvath; AgeAccelLevine; and AgeAccelGrim. Exposure variables included: relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores); and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0-2 years, weight gain only), early childhood (2-4 years), middle childhood (4-7 years) and late childhood to adolescence (7-15 years); age at menarche; and pubertal stage for men at 14-15 years. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study (NCDS).
RESULTS
A 1SD increase in relative weight gain in late childhood to adolescence was associated with 0.50 years (95% CI 0.20, 0.79) higher AgeAccelGrim. Although the CI includes the null, the estimate was similar in NCDS [0.57 years (95% CI - 0.01, 1.16)] There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥ 12 years had 1.20 years (95% CI 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche < 12 years; however, this was not replicated in NCDS and was not statistically significant after Bonferroni correction.
CONCLUSIONS
Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, we found rapid weight gain during pubertal development, previously related to higher cardiovascular disease risk, to be associated with older AgeAccelGrim. Given this is an exploratory study, this finding requires replication.
Topics: Adolescent; Adult; Age Factors; Aging; Biomarkers; Birth Weight; Body Height; Body Mass Index; Child; Child Development; Child, Preschool; DNA Methylation; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; United Kingdom; Weight Gain; Young Adult
PubMed: 34372922
DOI: 10.1186/s13148-021-01138-x -
Ecology Jul 2021Organismal locomotion mediates ecological interactions and shapes community dynamics. Locomotion is constrained by intrinsic and environmental factors and integrating...
Organismal locomotion mediates ecological interactions and shapes community dynamics. Locomotion is constrained by intrinsic and environmental factors and integrating these factors should clarify how locomotion affects ecology across scales. We extended general theory based on metabolic scaling and biomechanics to predict the scaling of five locomotor performance traits: routine speed, maximum speed, maximum acceleration, minimum powered turn radius, and angular speed. To test these predictions, we used phylogenetically informed analyses of a new database with 884 species and found support for our quantitative predictions. Larger organisms were faster but less maneuverable than smaller organisms. Routine and maximum speeds scaled with body mass to 0.20 and 0.17 powers, respectively, and plateaued at higher body masses, especially for maximum speed. Acceleration was unaffected by body mass. Minimum turn radius scaled to a 0.19 power, and the 95% CI included our theoretical prediction, as we predicted. Maximum angular speed scaled higher than predicted but in the same direction. We observed universal scaling among locomotor modes for routine and maximum speeds but the intercepts varied; flying organisms were faster than those that swam or ran. Acceleration was independent of size in flying and aquatic taxa but decreased with body mass in land animals, possibly due to the risk of injury large, terrestrial organisms face at high speeds and accelerations. Terrestrial mammals inhabiting structurally simple habitats tended to be faster than those in complex habitats. Despite effects of body size, locomotor mode, and habitat complexity, universal scaling of locomotory performance reveals the general ways organisms move across Earth's complex environments.
Topics: Animals; Biomechanical Phenomena; Body Size; Locomotion; Mammals
PubMed: 33864262
DOI: 10.1002/ecy.3369 -
Zoological Science Jun 2021Growth-retarded () mice display primary congenital hypothyroidism due to the hyporesponsiveness of their thyroid glands to thyroid-stimulating hormone (TSH). We examined...
Growth-retarded () mice display primary congenital hypothyroidism due to the hyporesponsiveness of their thyroid glands to thyroid-stimulating hormone (TSH). We examined somatic growth, anterior pituitary development, and hormonal profiles in female mice and normal ones. Although growth in females was suppressed 2 weeks after birth, the measured growth parameters and organ weights gradually increased and finally reached close to the normal levels. mice exhibited delayed eye and vaginal openings and remained in a state of persistent diestrus thereafter, plasma estrogen levels being lower than those in normal mice. mice that received normal-donor thyroids showed accelerated growth and their body weights increased up to the sham-normal levels, indicating the importance of early thyroid hormone supplementation. In the anterior pituitary, there were fewer growth hormone (GH) and prolactin (PRL) cells in mice than in normal mice as examined at 12 weeks after birth, but the numbers of these cells did not differ from those in normal mice after 24 weeks. mice had more TSH cells than normal mice until 48 weeks. Plasma GH levels in mice were lower than those in normal mice at 2 weeks, but did not differ substantially after 5 weeks. Compared with normal mice, mice had significantly lower plasma PRL and thyroxine levels, but notably higher TSH levels until 48 weeks. These findings indicate that thyroid hormone deficiency in mice causes delayed development and growth, and inappropriate development of GH, PRL and TSH cells, followed by the abnormal secretion of hormones by these pituitary cells.
Topics: Animals; Congenital Hypothyroidism; Female; Growth Hormone; Mice; Organ Size; Pituitary Gland; Prolactin; Thyroid Gland; Thyroid Hormones; Thyrotropin
PubMed: 34057348
DOI: 10.2108/zs200063 -
Scientific Reports Oct 2020Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, thus inhibiting necroptosis. In this current study, we have...
Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, thus inhibiting necroptosis. In this current study, we have investigated the possible involvement of necroptosis in the hair cycle regulation and further examined its underlying molecular mechanisms. Diverse RIPK1/3 inhibitors and siRNA were tested in the human outer-root sheath (ORS) cells and animal models. The expression and hair cycle-dependent expression of RIPK 1, respectively, were investigated in the hair follicles (HF) of human, pig, and the mouse. Resulting from the experiment, Nec-1s was most effective in the hair growth promotion among several inhibitors. Nec-1s induced the ORS cell proliferation and migration, and increased the HF length in mouse and pig organ cultures. In addition, it accelerated the telogen-to-anagen transition and elongated the anagen period in the mouse model. Both apoptosis and necroptosis were detected in hair cycle. RIPK1 and RIPK3 were highly expressed in ORS cells during the hair regression period. Nec-1s upregulated the mRNA expression of Wnt3a and Wnt5b, and the activity of β-catenin. Collectively, Nec-1s promotes hair growth through inhibiting necroptosis and activating the Wnt/β-catenin pathway. Necroptosis is involved in hair cycle regression, and Nec-1s is a promising target for hair-loss treatment.
Topics: Animals; Apoptosis; Cell Line; Cell Movement; Cell Proliferation; Hair; Hair Follicle; Humans; Imidazoles; Indoles; Male; Mice; Necroptosis; Swine; Wnt Signaling Pathway
PubMed: 33077863
DOI: 10.1038/s41598-020-74796-1 -
Cellular and Molecular Life Sciences :... Apr 2021In recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest... (Review)
Review
In recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called 'zombie cells' are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies.
Topics: Aging; Animals; Cell Proliferation; Cellular Senescence; Fibrosis; Humans; Immune System; Neoplasms; Translational Research, Biomedical; Wound Healing
PubMed: 33439271
DOI: 10.1007/s00018-020-03746-x -
Clinical Endocrinology Feb 2020Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities... (Review)
Review
Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.
Topics: Adrenal Gland Diseases; Age of Onset; Body Height; Child; Child Development; Endocrinology; Growth Disorders; Humans; Pediatrics; Practice Guidelines as Topic; Prevalence
PubMed: 31747461
DOI: 10.1111/cen.14131 -
Experimental & Molecular Medicine Jun 2023The tripartite motif (TRIM) 22 and mitogen-activated protein kinase (MAPK) signaling pathways play critical roles in the growth of glioblastoma (GBM). However, the...
The tripartite motif (TRIM) 22 and mitogen-activated protein kinase (MAPK) signaling pathways play critical roles in the growth of glioblastoma (GBM). However, the molecular mechanism underlying the relationship between TRIM22 and MAPK signaling remains unclear. Here, we found that TRIM22 binds to exon 2 of the sphingosine kinase 2 (SPHK2) gene. An ERK1/2-driven luciferase reporter construct identified TRIM22 as a potential activator of MAPK signaling. Knockout and overexpression of TRIM22 regulate the inhibition and activation of MAPK signaling through the RING-finger domain. TRIM22 binds to Raf-1, a negative regulator of MAPK signaling, and accelerates its degradation by inducing K48-linked ubiquitination, which is related to the CC and SPRY domains of TRIM22 and the C1D domain of Raf-1. In vitro and in vivo, an SPHK2 inhibitor (K145), an ERK1/2 inhibitor (selumetinib), and the nonphosphorylated mutant Raf-1 inhibited GBM growth. In addition, deletion of the RING domain and the nuclear localization sequence of TRIM22 significantly inhibited TRIM22-induced proliferation of GBM cells in vivo and in vitro. In conclusion, our study showed that TRIM22 regulates SPHK2 transcription and activates MAPK signaling through posttranslational modification of two critical regulators of MAPK signaling in GBM cells.
Topics: Humans; Mitogen-Activated Protein Kinases; Glioblastoma; Signal Transduction; Cell Line; Cell Proliferation; Minor Histocompatibility Antigens; Tripartite Motif Proteins; Repressor Proteins
PubMed: 37258577
DOI: 10.1038/s12276-023-01007-y -
Nature Reviews. Endocrinology Aug 2019
Topics: Acceleration; Aging; Cell Proliferation; Cellular Senescence; Diabetes Mellitus; Humans
PubMed: 31239521
DOI: 10.1038/s41574-019-0232-4 -
The Plant Journal : For Cell and... Mar 2023High yield and stress resistance are the major prerequisites for successful crop cultivation, and can be achieved by modifying plant architecture. Evolutionarily... (Review)
Review
High yield and stress resistance are the major prerequisites for successful crop cultivation, and can be achieved by modifying plant architecture. Evolutionarily conserved growth-regulating factors (GRFs) control the growth of different tissues and organs of plants. Here, we provide a systematic overview of the expression patterns of GRF genes and the structural features of GRF proteins in different plant species. Moreover, we illustrate the conserved and divergent roles of GRFs, microRNA396 (miR396), and GRF-interacting factors (GIFs) in leaf, root, and flower development. We also describe the molecular networks involving the miR396-GRF-GIF module, and illustrate how this module coordinates with different signaling molecules and transcriptional regulators to control development of different plant species. GRFs promote leaf growth, accelerate grain filling, and increase grain size and weight. We also provide some molecular insight into how coordination between GRFs and other signaling modules enhances crop productivity; for instance, how the GRF-DELLA interaction confers yield-enhancing dwarfism while increasing grain yield. Finally, we discuss how the GRF-GIF chimera substantially improves plant transformation efficiency by accelerating shoot formation. Overall, we systematically review the conserved and divergent roles of GRFs and the miR396-GRF-GIF module in growth regulation, and also provide insights into how GRFs can be utilized to improve the productivity and nutrient content of crop plants.
Topics: Plants, Genetically Modified; Gene Expression Regulation, Plant; MicroRNAs; Plant Development; Plant Leaves; Intercellular Signaling Peptides and Proteins
PubMed: 36582168
DOI: 10.1111/tpj.16090