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Journal of Marriage and the Family Jun 2020The present study investigated the factorial structure of the dyadic stress proliferation process in couples in enduring marriages leading to their psychological...
OBJECTIVE
The present study investigated the factorial structure of the dyadic stress proliferation process in couples in enduring marriages leading to their psychological distress in later years.
BACKGROUND
Stress proliferation during short and long periods of time has been shown to drive complex stress-distress processes during the life course. This research has largely been limited to individual-level stress proliferation with less research demonstrating stress proliferation in the context of enduring relationships.
METHODS
Using data from 224 dual-earner couples in long-term marriages, the present study examined the aggregation of individual stress (as defined by role-related stress experiences including provider, work, spousal, and parental roles) into couple-level stress constructs. These couple-level stress constructs were examined as predictors of husbands' and wives' psychological distress over 27 years (1991-2017) independent of individual-level stress.
RESULTS
Couple-level socioeconomic and relationship stress was highly stable over time, suggesting that stress within a domain proliferates across the life course. Individual-level psychological distress was significantly associated with couple-level stress constructs at midlife and in later life after controlling for previous distress.
CONCLUSION
Evidence suggests that husbands' and wives' psychological distress is significantly affected by couple-level stress processes. Findings have implications for intervention and prevention programs focusing on the well-being of married couples in later life.
PubMed: 34393266
DOI: 10.1111/jomf.12644 -
Pakistan Journal of Medical Sciences 2023Stanniocalcin-2 (STC2), a secreted glycoprotein that is involved in the regulation of angiogenesis, was proposed as one of the mechanisms of neovascularization in...
OBJECTIVE
Stanniocalcin-2 (STC2), a secreted glycoprotein that is involved in the regulation of angiogenesis, was proposed as one of the mechanisms of neovascularization in hemangioma (HA). We aimed to investigate the effect of STC2 on proliferation and angiogenesis in hemangioma-derived endothelial cells.
METHODS
The hemangioma samples from HA patients with the median age of six months were surgically collected in the Affiliated Hospital of Weifang Medical University from October 2019 to June 2021, and divided into normal skin tissues (n=10), involuting-phase HAs (n=10) and proliferating-phase HAs (n=10) according to the Mulliken classification. The expression of STC2 was detected in involuting-phase HAs and proliferating-phase HAs. Hemangioma endothelial cells (HemEC) were transfected with small interfering RNA (siRNA) specific for STC2, and cell survival and tube formation were analyzed.
RESULTS
STC2 expression in proliferating-phase HAs was markedly higher than in the normal skin tissues and involving-phase HAs. Similarly, STC2 expression was higher in HemEC compared to the control human umbilical vein endothelial cells (HUVEC). Knockdown of STC2 slowed the proliferation of HemEC and decreased the expression of proliferating cell nuclear antigen (PCNA) in HemEC. Moreover, knockdown of STC2 in HemEC inhibited vascular endothelial cell angiogenesis and regulated the expression and phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). Mechanistically, STC2 knockdown attenuated the activation of Akt/eNOS signaling, which was abolished by insulin growth factor-1 (IGF-1), the activator of Akt signaling, accompanying by increased proliferation and tube formation of HemEC.
CONCLUSION
Inhibition of STC2 suppresses HemEC proliferation and angiogenesis by VEGFR2/Akt/eNOS pathway, which warrants further development of STC2-based strategies for HA treatment.
PubMed: 37492297
DOI: 10.12669/pjms.39.4.7384 -
Stem Cell Research & Therapy Jul 2022To explore the function of phosphorylation of KAP1 (p-KAP1) at the serine-824 site (S824) in the proliferation and apoptosis of endogenous neural stem cells (NSCs) after...
AIMS
To explore the function of phosphorylation of KAP1 (p-KAP1) at the serine-824 site (S824) in the proliferation and apoptosis of endogenous neural stem cells (NSCs) after cerebral ischemic/reperfusion (I/R).
METHODS
The apoptosis and proliferation of C17.2 cells transfected with the p-KAP1-expression plasmids and the expression of proliferation cell nuclear antigen (PCNA) and p-KAP1 were detected by immunofluorescence and Western blotting after the Oxygen Glucose deprivation/reperfusion model (OGD/R). The interaction of p-KAP1 and CUL4A with PCNA was analyzed by immunoprecipitation. In the rats MCAO model, we performed the adeno-associated virus (AAV) 2/9 gene delivery of p-KAP1 mutants to verify the proliferation of endogenous NSCs and the colocalization of PCNA and CUL4A by immunofluorescence.
RESULTS
The level of p-KAP1 was significantly down-regulated in the stroke model in vivo and in vitro. Simulated p-KAP1(S824) significantly increased the proliferation of C17.2 cells and the expression of PCNA after OGD/R. Simulated p-KAP1(S824) enhanced the binding of p-KAP1 and PCNA and decreased the interaction between PCNA and CUL4A in C17.2 cells subjected to OGD/R. The AAV2/9-mediated p-KAP1(S824) increased endogenous NSCs proliferation, PCNA expression, p-KAP1 binding to PCNA, and improved neurological function in the rat MCAO model.
CONCLUSIONS
Our findings confirmed that simulated p-KAP1(S824) improved the survival and proliferation of endogenous NSCs. The underlying mechanism is that highly expressed p-KAP1(S824) promotes binding to PCNA, and inhibits the binding of CUL4A to PCNA. This reduced CUL4A-mediated ubiquitination degradation to increase the stability of PCNA and promote the survival and proliferation of NSCs.
Topics: Animals; Antigens, Nuclear; Brain Ischemia; Ischemia; Neural Stem Cells; Phosphorylation; Proliferating Cell Nuclear Antigen; Rats; Reperfusion Injury; Transcription Factors; Tripartite Motif-Containing Protein 28
PubMed: 35799276
DOI: 10.1186/s13287-022-02962-5 -
Diabetes & Metabolism Journal Jan 2024Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the...
Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification.
BACKGRUOUND
Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system.
METHODS
To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide.
RESULTS
Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs.
CONCLUSION
These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.
Topics: Humans; Angiotensin II; Exenatide; Liraglutide; Muscle, Smooth, Vascular; Proliferating Cell Nuclear Antigen; Glucagon-Like Peptide Receptors; Diabetes Mellitus, Type 2; Phosphatidylinositol 3-Kinases; Phosphates; Cell Proliferation; Vascular Calcification
PubMed: 38173373
DOI: 10.4093/dmj.2022.0363 -
Bio-medical Materials and Engineering 2021Merging stem cells with biomimetic materials represent an attractive approach to tissue engineering. The development of an alternative scaffold with the ability to mimic...
BACKGROUND
Merging stem cells with biomimetic materials represent an attractive approach to tissue engineering. The development of an alternative scaffold with the ability to mimic the extracellular matrix, and the 3D gradient preventing any alteration in cell metabolism or in their gene expression patterns, would have many medical applications.
OBJECTIVE
In this study, we introduced the use of RGD (Arg-Gly-Asp) bio-conjugated cotton to promote the growth and proliferation of mesenchymal stem cells (MSCs).
METHODS
We measured the expression of stem cell markers and adhesion markers with Q-PCR and analyzed the transcriptomic. The results obtained showed that the MSCs, when cultured with bio-conjugated cotton fibers, form aggregates around the fibers while proliferating. The seeded MSCs with cotton fibers proliferated in a similar fashion to the cells seeded on the monolayer (population doubling level 1.88 and 2.19 respectively).
RESULTS
The whole genome sequencing of cells adhering to these cotton fibers and cells adhering to the cell culture dish showed differently expressed genes and pathways in both populations. However, the expression of the stem cell markers (Oct4, cKit, CD105) and cell adhesion markers (CD29, HSPG2 and CD138), when examined with quantitative RT-PCR, was maintained in both cell populations.
CONCLUSION
These results clearly show the ability of the cotton fibers to promote MSCs growth and proliferation in a 3D structure mimicking the in vivo environment without losing their stem cell phenotype.
Topics: Cell Differentiation; Cell Proliferation; Cells, Cultured; Cotton Fiber; Mesenchymal Stem Cells; Oligopeptides; Tissue Scaffolds
PubMed: 33164919
DOI: 10.3233/BME-201115 -
Neurotoxicology Jul 2023Zebrafish is known for its widespread neurogenesis and regenerative capacity, as well as several biological advantages, which turned it into a relevant animal model in...
Zebrafish is known for its widespread neurogenesis and regenerative capacity, as well as several biological advantages, which turned it into a relevant animal model in several areas of research, namely in toxicological studies. Ketamine is a well-known anesthetic used both in human as well as veterinary medicine, due to its safety, short duration and unique mode of action. However, ketamine administration is associated with neurotoxic effects and neuronal death, which renders its use on pediatric medicine problematic. Thus, the evaluation of ketamine effects administration at early stages of neurogenesis is of pivotal importance. The 1-41-4 somites stage of zebrafish embryo development corresponds to the beginning of segmentation and formation of neural tube. In this species, as well as in other vertebrates, longitudinal studies are scarce, and the evaluation of ketamine long-term effects in adults is poorly understood. This study aimed to assess the effects of ketamine administration at the 1-4 somites stage, both in subanesthetic and anesthetic concentrations, in brain cellular proliferation, pluripotency and death mechanisms in place during early and adult neurogenesis. For that purpose, embryos at the 1-4 somites stage (10.5 h post fertilization - hpf) were distributed into study groups and exposed for 20 min to ketamine concentrations at 0.2/0.8 mg/mL. Animals were grown until defined check points, namely 50 hpf, 144 hpf and 7 months adults. The assessment of the expression and distribution patterns of proliferating cell nuclear antigen (PCNA), of sex-determining region Y-box 2 (Sox 2), apoptosis-inducing factor (AIF) and microtubule-associated protein 1 light chain 3 (LC3) was performed by Western-blot and immunohistochemistry. The results evidenced the main alterations in 144 hpf larvae, namely in autophagy and in cellular proliferation at the highest concentration of ketamine (0.8 mg/mL). Nonetheless, in adults no significant alterations were seen, pointing to a return to a homeostatic stage. This study allowed clarifying some of the aspects pertaining the longitudinal effects of ketamine administration regarding the CNS capacity to proliferate and activate the appropriate cell death and repair mechanisms leading to homeostasis in zebrafish. Moreover, the results indicate that ketamine administration at 1-4 somites stage in the subanesthetic and anesthetic concentrations despite some transitory detrimental effects at 144 hpf, is long-term safe for CNS, which are newly and promising results in this research field.
Topics: Animals; Child; Humans; Ketamine; Zebrafish; Anesthetics, Dissociative; Cell Death; Cell Proliferation; Embryo, Nonmammalian
PubMed: 37196828
DOI: 10.1016/j.neuro.2023.05.008 -
Oral Diseases May 2022To investigate Sonic hedgehog (Shh) effects on proliferation and apoptosis of tongue epithelial cells in embryonic and ageing mice.
OBJECTIVE
To investigate Sonic hedgehog (Shh) effects on proliferation and apoptosis of tongue epithelial cells in embryonic and ageing mice.
MATERIALS AND METHODS
Embryonic day 13.5 (E13.5), E14.5, E16.5 and postnatal day 0.5 (PN0.5) K14-Cre;Shh mice, and E14.5, E16.5, PN0.5, PN90.5 and postnatal 1.5 years (PN1.5Y) wild-type (Wt) mice were employed. Scanning electron microscopy, haematoxylin-eosin and immunohistochemistry were performed. Gel beads containing exogenous Shh protein were embedded in the tongue of PN90.5 and PN1.5Y Wt mice. Three days later, 5-bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA) immunohistochemical and TUNEL staining were performed.
RESULTS
The number of fungiform papillae was decreased with age. The numbers of BrdU- and PCNA-positive cells were the highest at PN0.5 and the lowest at PN1.5Y. Compared with Wt mice, K14-Cre;Shh mice had decreased PCNA-positive cells in the epithelium, a smaller tongue volume, and fewer papillae at PN0.5. At E14.5, the number of BrdU-positive cells was decreased in K14-Cre;Shh mice. At PN1.5Y, the number of apoptotic cells in tongue tissue exposed to Shh protein was less than that in the BSA group and the numbers of BrdU- and PCNA-positive proliferating cells were increased.
CONCLUSION
Shh maintains cell proliferation and reduces apoptosis during tongue development and ageing.
Topics: Animals; Bromodeoxyuridine; Cell Proliferation; Epithelial Cells; Hedgehog Proteins; Mice; Proliferating Cell Nuclear Antigen; Signal Transduction; Tongue
PubMed: 33751723
DOI: 10.1111/odi.13836 -
The Journal of Clinical Investigation Nov 2023BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact...
BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact proviruses in elite controllers (ECs) and people on long-term therapy suggest that proviruses in specific chromosomal locations can evade immune surveillance. However, direct evidence of this mechanism is missing.METHODSIn this case report, we characterized integration sites and full genome sequences of expanded T cell clones in an EC before and after chemoradiation. We identified the cognate peptide of infected clones to investigate cell proliferation and virus production induced by T cell activation, and susceptibility to autologous CD8+ T cells.RESULTSThe proviral landscape was dominated by 2 large clones with replication-competent proviruses integrated into zinc finger (ZNF) genes (ZNF470 and ZNF721) in locations previously associated with deeper latency. A third nearly intact provirus, with a stop codon in Pol, was integrated into an intergenic site. Upon stimulation with cognate Gag peptides, infected clones proliferated extensively and produced virus, but the provirus in ZNF721 was 200-fold less inducible. While autologous CD8+ T cells decreased the proliferation of cells carrying the intergenic provirus, they had no effect on cells with the provirus in the ZNF721 gene.CONCLUSIONSWe provide direct evidence that upon activation of infected clones by cognate antigen, the lower inducibility of intact proviruses in ZNF genes can result in immune evasion and persistence.FUNDINGOffice of the NIH Director and National Institute of Dental & Craniofacial Research; NIAID, NIH; Johns Hopkins University Center for AIDS Research.
Topics: Humans; HIV-1; HIV Infections; Proviruses; CD4-Positive T-Lymphocytes; Clone Cells; Virus Latency
PubMed: 37698927
DOI: 10.1172/JCI171097 -
Biomedicine & Pharmacotherapy =... Oct 2019Hypoxia has been suggested to be both beneficial and harmful to the proliferation of cardiomyocytes. This controversy remains unresolved, and the underlying mechanism by...
BACKGROUND
Hypoxia has been suggested to be both beneficial and harmful to the proliferation of cardiomyocytes. This controversy remains unresolved, and the underlying mechanism by which hypoxia exerts its effects remains unclear. We here hypothesize that cardiomyocyte developmental stage may play a role.
METHODS AND RESULTS
The embryonic ventricular myocyte cell line H9C2, primary isolated fetal cardiomyocytes, and neonatal cardiomyocytes were cultured with normal O (21% O) or under hypoxic conditions (10% O) for 7 days, and then harvested for Western blotting, qRT-PCR, and immunostaining. When cultured under hypoxic conditions, proliferating marker-Ki67, mRNA level, and the percentage of Ki67-positive cardiomyocytes were significantly lower in H9C2 and fetal cardiomyocytes but higher in neonatal cardiomyocytes. Consistently, the mRNA and protein levels and induced nuclear localization of yes associated protein 1(YAP1), one of the most important regulators of cardiomyocyte proliferation, were significantly lower in H9C2 and fetal cardiomyocytes but up-regulated in neonatal cardiomyocytes when treated with hypoxia. Compared to neonatal cardiomyocytes, there was a lower level of troponin T mRNA and protein expression in H9C2 and fetal cardiomyocytes. When H9C2 or fetal cardiomyocytes overexpressing troponin T in were cultured under hypoxic condition, their ability to proliferate increased.
CONCLUSIONS
The effect of hypoxia on the proliferation of cardiomyocyte is associated with their developmental stage. YAP1 expression is positively correlated with the change in cardiomyocyte proliferation in response to hypoxia. Developmental stage- specific sarcomere component troponin T may partly account for the underlying mechanism.
Topics: Animals; Animals, Newborn; Apoptosis Regulatory Proteins; Cell Hypoxia; Cell Line; Cell Proliferation; Cells, Cultured; Models, Biological; Myocytes, Cardiac; Rats; Troponin T; YAP-Signaling Proteins
PubMed: 31545287
DOI: 10.1016/j.biopha.2019.109391 -
Transplantation May 2022Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T...
BACKGROUND
Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T cells in response to PECs and to explore the immuno-modulation of B7 and mammalian target of rapamycin blockade of T cells and/or PECs during xeno-responses.
METHODS
Rapid memory T-cell (TM) responses to PECs were assessed by an intracellular cytokine staining. T-cell proliferation to PEC with or without belatacept or rapamycin was evaluated by a mixed lymphocyte-endothelial cell reaction (MLER). Additionally, rapamycin-pretreated PECs were used in MLER. Cell phenotypes were analyzed by flow cytometry.
RESULTS
Tumor necrosis factor-α/interferon-γ producers were detected in CD8+ cells stimulated by human endothelium but not PECs. MLER showed proliferation of CD4+ and CD8+ cells with predominantly memory subsets. Purified memory and naive cells proliferated following PEC stimulation with an increased frequency of TM in PEC-stimulated naive cells. Proliferating cells upregulated programmed cell death-1 (PD-1) and CD2 expression. Belatacept partially inhibited T-cell proliferation with reduced CD2 expression and frequency of the CD8+CD2highCD28- subset. Rapamycin dramatically inhibited PEC-induced T-cell proliferation, and rapamycin-preconditioned PECs failed to induce T-cell proliferation. PD-1 blockade did not restore T-cell proliferation to rapamycin-preconditioned PECs.
CONCLUSIONS
Humans lack rapid TM-mediated responses to PECs but induce T-cell proliferative responses characterized largely as TM with increasing CD2 and PD-1 expression. B7-CD28 and mammalian target of rapamycin blockade of T cells exhibit dramatic inhibitory effects in altering xeno-proliferating cells. Rapamycin alters PEC xeno-immunogenicity leading to inhibition of xeno-specific T-cell proliferation independent of PD-1-PD ligand interaction.
Topics: Abatacept; Animals; B7 Antigens; Cell Proliferation; Endothelial Cells; Humans; Mammals; Programmed Cell Death 1 Receptor; Sirolimus; Swine; TOR Serine-Threonine Kinases
PubMed: 34387242
DOI: 10.1097/TP.0000000000003920