Biology subjects

Oliveira, C. R.

Publications and source records attributed to Oliveira, C. R..

5 recordsLinked to original sources

bioRxiv2026

Reproductive experience promotes permanent body growth independently of growth hormone

Pregnancy leads to many adaptations in the maternal body, some of which are reversible. However, reproductive experience can also result in permanent effects. Here, we investigated how pregnancy influences the somatotrophic system and the lasting effects of reproductive experience on the maternal organism. Reproductive experience induced a pronounced increase in lean body mass and longitudinal growth in both wild-type and growth hormone (GH)-deficient mice compared with age-matched virgins. Body growth was primarily observed during the first pregnancy, whereas a second gestation was mostly associated with increased adiposity. Increased GH secretion was observed in pregnant wild-type mice but not in pregnant GHRHR-deficient mice. Pregnancy-induced body growth is preserved despite disruption of GH-, ghrelin-, and estrogen-related signaling pathways. Data from a cohort of women with isolated GH deficiency (IGHD) caused by a loss-of-function mutation in the GHRHR gene revealed that nulliparous women were 7 cm shorter than those with one or more pregnancies. In conclusion, reproductive experience induces permanent changes in the maternal organism, promoting body growth in models that allow this response. Pregnancy-induced body growth appears to be independent of GH action. These findings underscore the need for further studies to investigate the long-lasting consequences of reproductive experience in females.

physiology↗

bioRxiv2021

Tig1 regulates proximo-distal identity during salamander limb regeneration

Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed positional identity. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.

developmental biology↗

bioRxiv2020

Immunoregulatory effects of Imuno TF (transfer factors) on Th1/Th2/Th17/Treg cytokines

Transfer factors are known since 1955 due to their activities on the immune system. Although the reports on the effects on diverse immune mechanisms, their role on Th1, Th2, Th17 and Treg responses was still not described. In this sense, the present work focused on the evaluation of such immune responses. For that, human lymphocytes, and mice thymic, splenic and Peyers cells were stimulated with Lipopolysaccharides and Concanavalin A, and then treated with isolated transfer factors (Imuno TF(R)). The culture medium was harvested and the quantification of Th1 cytokines (IL-2 and IFN-{gamma}), Th2 cytokines (IL-4, IL-5, and IL-13), Th17 cytokine (IL- 17), Treg cytokine (IL-35), inflammatory cytokines (IL-6 and TNF-), and anti-inflammatory cytokine (IL-10) was performed, as well as the quantification of mRNA levels. Imuno TF(R) positively regulated Th1 cytokines, while decreased Th2 cytokines. It also increased levels of mRNA and secretion of the anti-inflammatory cytokine IL-10, whereas it reduced levels of mRNA and the secretion of pro-inflammatory cytokines IL-6 and TNF-. Finally, it reversed the hypersecretion of IL-17 and did not promote significant changes in IL-35 secretion. This highlights the role of Imuno TF(R) in the regulation of the immune responses.

immunology↗

bioRxiv2020

Senotherapeutic peptide reduces skin biological age and improves skin health

Skin aging has been primarily related to aesthetics and beauty. Therefore, interventions have focused on reestablishing skin appearance, but not necessarily skin health, function, and resilience. Recently, cellular senescence was shown to play a role in age-related skin function deterioration and influence organismal health and, potentially, longevity. In the present study, a two-step screening was performed to identify peptides capable of reducing cellular senescence in human dermal fibroblasts (HDF) from Hutchinson-Gilford Progeria (HGPS) patients. From the top four peptides of the first round of screening, we built a 764-peptide library using amino acid scanning, of which the second screen led to the identification of peptide 14. Peptide 14 effectively decreased HDF senescence induced by HGPS, chronological aging, ultraviolet-B radiation, and etoposide treatment, without inducing significant cell death, and likely by modulating longevity and senescence pathways. We further validated the effectiveness of peptide 14 using human skin equivalents and skin biopsies, where peptide 14 promoted skin health and reduced senescent cell markers, as well as the biological age of samples, according to the Skin-Specific DNA methylation clock, MolClock. Topical application of peptide 14 outperformed Retinol treatment, the current gold-standard in "anti-aging" skin care. Finally, we determined that peptide 14 is safe for long-term applications and also significantly extends both the lifespan and healthspan of C. elegans worms tested in two independent testings. This highlights the potential for geroprotective applications of the senotherapeutic compounds identified using our screening platform beyond the skin.

bioengineering↗

bioRxiv2019

Dosing regimen of gentamicin and the effect of antenatal steroids on clearance in preterm infants

ObjectiveDetermine the gentamicin pharmacokinetic and pharmacodynamic (PK/PD) profiles of once daily dosing (ODD) versus every 18-hour (q18h) regimens and to characterize the effect of antenatal steroid on gentamicin clearance (GentCL).\n\nStudy DesignRetrospective cohort of preterm infants ([≤]34 weeks gestation; [≤]7 days) who received gentamicin for >48 hours from January 2005 to June 2007. Serum gentamicin peak and trough concentrations were determined, and PK/PD profiles calculated using standard noncompartmental methods.\n\nResult122 (63%) infants received ODD and 73 (37%) received q18h regimen. Desired gentamicin peak (5 to 12 mcg/mL) and trough (<2 mcg/mL) concentrations were achieved in 80% (95%CI, 72-86) on ODD vs. 47% (95%CI, 36-58) on q18h (p<0.001). Target drug exposure (AUC >72 mcg/mL/hr) was achieved in 73% (89/122) of infants on ODD vs. 22% (16/73) on q18h (p < 0.001). GentCL was significantly lower in those who receive antenatal steroid (37+/-8 mL/kg/hr vs. 42+/-13 mL/kg/hr, p=0.04) but not affected by postnatal indomethacin treatment (p>0.86).\n\nConclusionPK/PD profile of gentamicin is improved by ODD in preterm infants. GentCl was significantly less in infants exposed to antenatal steroids but not in those treated with indomethacin.

pharmacology and toxicology↗