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1.
Oral Dis ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566281

RESUMO

OBJECTIVE: To characterize the distribution of macrophages, neutrophils, NK cells, and blood vessels in peri-implantitis compared to healthy aged gingiva samples. MATERIALS AND METHODS: This observational study included eight gingival samples from peri-implantitis and eight from periodontally healthy individuals. By immunofluorescence were identified neutrophils, NK cells, macrophages, and their pro-inflammatory or pro-healing phenotypes, and blood vessels. Two ROIs were designated as zone 1, connective tissue closest to the epithelium and zone 2, connective tissue over 200 microns from the rete ridges. Immune cells and vascular structures were quantified and characterized according to their distribution in both zones. RESULTS: Two peri-implantitis zones were characterized by unique macrophage phenotypes and blood vessel architecture. Blood vessels were larger in zone 2 in peri-implantitis. A greater number of NK cells and macrophages were found in peri-implantitis compared to healthy aged samples. A higher presence of pro-inflammatory macrophages was found in zone 1 compared to zone 2. A similar proportion of pro-inflammatory and pro-healing macrophages were found in zone 2. CONCLUSION: A specific distribution for pro-inflammatory macrophages and vascular architecture is observed in peri-implantitis. TNF-α colocalizes with macrophages in the connective tissue near rete ridges. NK cells are more abundant in peri-implantitis than in healthy samples.

2.
BMC Anesthesiol ; 24(1): 329, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289610

RESUMO

BACKGROUND: To examine the relationship between neutrophil-to-lymphocyte ratio (NLR), age, and mortality rates after emergency surgery. METHODS: In this observational study, a total of 851 patients undergoing emergency surgery between January 2022 and January 2023 were retrospective examined. Using 30 and 180 days mortality data, NLR differences and receiver operating characteristic (ROC) curves were analyzed using a 65-year threshold. A multiple logistic regression model was constructed incorporating age and NLR. Finally, Kaplan-Meier curves were constructed for mortality. RESULTS: Among 851 patients, the 30 and 180 days mortality rates were 5.2% and 10.8%, respectively. Median NLR in 30 days was 5.6 (3.1 to 9.6) in survivors and 8.7 (4.6 to 13.4) in deceased patients (p < 0.0001); in 180 days, it was 5.5 (3.1 to 9.8) and 8.8 (4.8 to 14.5), respectively (p < 0.0001). In the 30- and 180-days mortality analyses, median NLRs were 5.1 (2.9 to 8.9) and 4.9 (2.9 to 8.8) in survivors and 10.6 (6.9 to 16.6) and 9.3 (5.4 to 14.9) in deceased patients aged < 65 years, respectively. The ROC AUC in patients younger than 65 years was higher for 30 days (AUC 0.75; 95% CI 0.72 to 0.87) and 180 days (AUC 0.73; 95% CI 0.64 to 0.81). Multivariate logistic regression revealed that the NLR (odds ratio, 1.03 [95% CI 1.005 to 1.053; p = 0.0133) and age (odds ratio, 1.05 [95% CI 1.034 to 1.064; p < 0.0001) significantly contributed to the model. Survival analysis revealed differences in the 180 days mortality (p = 0.0006). CONCLUSION: We observed differences in preoperative NLR between patients who survived and those who died after emergency surgery. Age impacts the use of NLR as a mortality risk factor. TRIAL REGISTRATION: NCT06549101, retrospectively registered.


Assuntos
Linfócitos , Neutrófilos , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores Etários , Curva ROC , Contagem de Linfócitos , Emergências , Contagem de Leucócitos
3.
FASEB J ; 35(5): e21597, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33908663

RESUMO

Aging is a gradual biological process characterized by a decrease in cellular and organism functions. Aging-related processes involve changes in the expression and activity of several proteins. Here, we identified the transmembrane protease serine 11a (TMPRSS11a) as a new age-specific protein that plays an important role in skin wound healing. TMPRSS11a levels increased with age in rodent and human skin and gingival samples. Strikingly, overexpression of TMPRSS11a decreased cell migration and spreading, and inducing cellular senescence. Mass spectrometry, bioinformatics, and functional analyses revealed that TMPRSS11a interacts with integrin ß1 through an RGD sequence contained within the C-terminal domain and that this motif was relevant for cell migration. Moreover, TMPRSS11a was associated with cellular senescence, as shown by overexpression and downregulation experiments. In agreement with tissue-specific expression of TMPRSS11a, shRNA-mediated downregulation of this protein improved wound healing in the skin, but not in the skeletal muscle of old mice, where TMPRSS11a is undetectable. Collectively, these findings indicate that TMPRSS11a is a tissue-specific factor relevant for wound healing, which becomes elevated with aging, promoting cellular senescence and inhibiting cell migration and skin repair.


Assuntos
Envelhecimento/patologia , Movimento Celular , Fibroblastos/patologia , Proteínas de Membrana/metabolismo , Serina Proteases/metabolismo , Pele/patologia , Cicatrização , Adolescente , Adulto , Idoso , Envelhecimento/metabolismo , Animais , Proliferação de Células , Fibroblastos/metabolismo , Gengiva/metabolismo , Gengiva/patologia , Humanos , Proteínas de Membrana/genética , Camundongos , Pessoa de Meia-Idade , Serina Proteases/genética , Transdução de Sinais , Pele/metabolismo , Adulto Jovem
4.
FASEB J ; 34(6): 7847-7865, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32301552

RESUMO

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+ -activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4-interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular/fisiologia , Canais de Potássio/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Mama/metabolismo , Mama/patologia , Células COS , Linhagem Celular , Linhagem Celular Tumoral , Chlorocebus aethiops , Feminino , Células HEK293 , Humanos , Células MCF-7 , Prognóstico , Ubiquitina-Proteína Ligases/metabolismo
5.
BMC Oral Health ; 21(1): 106, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750358

RESUMO

BACKGROUND: This study aimed to evaluate the biological response of human apical papilla cells to different calcium hydroxide formulations and three tricalcium silicate-based materials. METHODS: Primary cells were obtained from explants of young immature premolars. 20,000 cells adhered for 24 h over discs of Biodentine™, ProRoot®MTA, BioRoot®RCS and calcium hydroxide mixed either with sodium chloride 0.9%w/v or polyethylene glycol and UltraCal® were used to evaluate cell adhesion by scanning electron microscopy and cell viability by MTT assay. RESULTS: Cells adhered to ProRoot®MTA showed an increase of F-actin like protrusions, suggesting bioactivity. Cells adhered to UltraCal® show protrusion such as filopodia. On the contrary, cells adhered to BioRoot®RCS showed no signs of any cellular protrusion. Regarding viability between the materials, we found a higher percentage of viability in cells cultured over discs of Biodentine™ and ProRoot®MTA. CONCLUSION: ProRoot®MTA and Biodentine™ exhibit a better cellular response of human apical papilla cells in vitro conditions compared to BioRoot® and calcium hydroxide diluted in sodium chloride.


Assuntos
Hidróxido de Cálcio , Materiais Restauradores do Canal Radicular , Compostos de Alumínio/farmacologia , Compostos de Cálcio/farmacologia , Hidróxido de Cálcio/farmacologia , Combinação de Medicamentos , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Óxidos , Silicatos/farmacologia
6.
FASEB J ; 33(8): 9434-9452, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31112396

RESUMO

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated nonselective cationic channel involved in a wide variety of physiologic and pathophysiological processes. Bioinformatics analyses of the primary sequence of TRPM4 allowed us to identify a putative motif for interaction with end-binding (EB) proteins, which are microtubule plus-end tracking proteins. Here, we provide novel data suggesting that TRPM4 interacts with EB proteins. We show that mutations of the putative EB binding motif abolish the TRPM4-EB interaction, leading to a reduced expression of the mature population of the plasma membrane channel and instead display an endoplasmic reticulum-associated distribution. Furthermore, we demonstrate that EB1 and EB2 proteins are required for TRPM4 trafficking and functional activity. Finally, we demonstrated that the expression of a soluble fragment containing the EB binding motif of TRPM4 reduces the plasma membrane expression of the channel and affects TRPM4-dependent focal adhesion disassembly and cell invasion processes.-Blanco, C., Morales, D., Mogollones, I., Vergara-Jaque, A., Vargas, C., Álvarez, A., Riquelme, D., Leiva-Salcedo, E., González, W., Morales, D., Maureira, D., Aldunate, I., Cáceres, M., Varela, D., Cerda, O. EB1- and EB2-dependent anterograde trafficking of TRPM4 regulates focal adhesion turnover and cell invasion.


Assuntos
Adesões Focais/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Biotinilação/fisiologia , Células COS , Adesão Celular/genética , Adesão Celular/fisiologia , Linhagem Celular , Movimento Celular/genética , Movimento Celular/fisiologia , Chlorocebus aethiops , Eletrofisiologia , Imunofluorescência , Humanos , Immunoblotting , Proteínas Associadas aos Microtúbulos/genética , Simulação de Dinâmica Molecular , Mutação/genética , Plasmídeos/genética , Canais de Cátion TRPM/genética
7.
BMC Anesthesiol ; 20(1): 121, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434495

RESUMO

BACKGROUND: The glycocalyx layer is a key structure in the endothelium. Tourniquet-induced ischemic periods are used during orthopedic surgery, and the reactive oxygen species generated after ischemia-reperfusion may mediate the shedding of the glycocalyx. Here, we describe the effects of tourniquet-induced ischemia-reperfusion and compare the effects of sevoflurane and propofol on the release of endothelial biomarkers after ischemia-reperfusion in knee-ligament surgery. METHODS: This pilot, single-center, blinded, randomized, controlled trial included 16 healthy patients. After spinal anesthesia, hypnosis was achieved with sevoflurane or propofol according to randomization. During the perioperative period, five venous blood samples were collected for quantification of syndecan-1, heparan sulfate, and thrombomodulin from blood serum by using ELISA assays kits. Sample size calculation was performed to detect a 25% change in the mean concentration of syndecan-1 with an alpha of 0.05 and power of 80%. RESULTS: For our primary outcome, a two-way ANOVA with post-hoc Bonferroni correction analysis showed no differences in syndecan-1 concentrations between the sevoflurane and propofol groups at any time point. In the sevoflurane group, we noted an increase in syndecan-1 concentrations 90 min after tourniquet release in the sevoflurane group from 34.6 ± 24.4 ng/mL to 47.9 ± 29.8 ng/mL (Wilcoxon test, p < 0.01) that was not observed in patients randomized to the propofol group. The two-way ANOVA showed no intergroup differences in heparan sulfate and thrombomodulin levels. CONCLUSIONS: Superficial endothelial damage without alterations in the cell layer integrity was observed after tourniquet knee-ligament surgery. There was no elevation in serum endothelial biomarkers in the propofol group patients. Sevoflurane did not show the protective effect observed in in vitro and in vivo studies. TRIAL REGISTRATION: The trial was registered in www.clinicaltrials.gov (ref: NCT03772054, Registered 11 December 2018).


Assuntos
Endotélio/efeitos dos fármacos , Joelho/cirurgia , Ligamentos/cirurgia , Propofol/farmacologia , Sevoflurano/farmacologia , Torniquetes/efeitos adversos , Adulto , Endotélio/química , Glicocálix/efeitos dos fármacos , Heparitina Sulfato/sangue , Humanos , Projetos Piloto , Traumatismo por Reperfusão/prevenção & controle , Sindecana-1/sangue
8.
Pflugers Arch ; 467(8): 1723-1732, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25231975

RESUMO

Transient receptor potential melastatin-like 4 (TRPM4) is a Ca(2+)-activated non-selective cation channel expressed in a wide range of human tissues. TRPM4 participates in a variety of physiological processes such as T cell activation, myogenic vasoconstriction, and allergic reactions. TRPM4 Ca(2+) sensitivity is enhanced by calmodulin (CaM) and phosphathydilinositol 4, 5-bisphosphate (PI(4,5)P2) binding, as well as, under certain conditions, PKC activation. However, information as to the mechanisms of modulation of this channel remains unknown, including direct identification of phosphorylation sites on TRPM4 and their role in channel features. Here, we use mass-spectrometric-based proteomic approaches (immunoprecipitation and tandem mass spectrometry) to unambiguously identify S839 as a phosphorylation site present on human TRPM4 expressed in a human cell line. Site-directed mutagenesis employing a serine to alanine mutation to eliminate phosphorylation, and a phospho-mimetic aspartate mutation, as well as biochemical and immunocytochemical experiments, revealed a role for S839 phosphorylation in the basolateral expression of TRPM4 channels in epithelial cells. Moreover, we demonstrated that casein kinase 1 (CK1) phosphorylates S839 and is responsible for the basolateral localization of TRPM4.


Assuntos
Caseína Quinase I/metabolismo , Canais de Cátion TRPM/metabolismo , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Células HEK293 , Humanos , Imunoprecipitação , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação , Fosforilação , Transporte Proteico , Proteômica/métodos , Serina , Canais de Cátion TRPM/química , Canais de Cátion TRPM/genética , Espectrometria de Massas em Tandem , Transfecção
9.
Microvasc Res ; 98: 187-96, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24518820

RESUMO

A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases.


Assuntos
Células Endoteliais/citologia , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPM/metabolismo , Adesão Celular , Movimento Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/química , Inflamação/metabolismo , Estresse Oxidativo , RNA Interferente Pequeno/metabolismo
10.
Periodontol 2000 ; 67(1): 234-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25494603

RESUMO

Growth factors play critical roles in periodontal repair through the regulation of cell behavior. Many of the cell responses regulated by these proteins include cell adhesion, migration, proliferation and differentiation. Periodontal regeneration involves an organized response of different cells, tissues and growth factors implicated in the coordination of these events. However, periodontal tissue reconstruction is an extremely difficult task. Multiple studies have been performed to understand the specific role of growth factors in periodontal wound healing. In the present review we analyze the evidence that supports the roles of growth factors in periodontal wound healing and regeneration.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Periodonto/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Periodontia/métodos , Periodonto/citologia , Periodonto/fisiologia , Plasma Rico em Plaquetas/metabolismo , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Células-Tronco/efeitos dos fármacos , Cicatrização/fisiologia
11.
Commun Biol ; 7(1): 811, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965360

RESUMO

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.


Assuntos
Encéfalo , Senescência Celular , Herpes Simples , Herpesvirus Humano 1 , Esclerose Múltipla , Animais , Camundongos , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/metabolismo , Esclerose Múltipla/virologia , Esclerose Múltipla/patologia , Esclerose Múltipla/metabolismo , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 1/patogenicidade , Herpes Simples/virologia , Herpes Simples/patologia , Feminino , Camundongos Endogâmicos C57BL , Encefalomielite Autoimune Experimental/virologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/metabolismo , Fenótipo , Sistema Nervoso Central/virologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Medula Espinal/virologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Biomarcadores/metabolismo , Encefalite por Herpes Simples/virologia , Encefalite por Herpes Simples/patologia , Encefalite por Herpes Simples/metabolismo
12.
Front Oncol ; 14: 1403089, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807771

RESUMO

Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis' virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.

13.
Front Nutr ; 11: 1380315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549747

RESUMO

Introduction: Energy imbalance gap (EIG) is defined as the average daily difference between energy intake (EI) and energy expenditure (EE). This study aimed to examine the associations between EIG and sociodemographic and anthropometric variables in the adolescent population of eight Latin America countries. Methods: A total of 680 adolescents aged 15 to 18 were included in this study. The estimation of EI was based on two non-consecutive 24-h dietary recalls. EE was predicted from Schofield equations using physical activity level obtained through the long version of the International Physical Activity Questionnaire. Sociodemographic data and anthropometric measurements were also obtained. A descriptive analysis and multilevel linear regression models were used to examine associations between variables. Results: The mean EI, EE, and EIG were 2091.3 kcal, 2067.8 kcal, and 23.5 kcal, respectively. Argentina had the highest EI and EIG, whereas Chile had the lowest EI and EIG. Males had a higher EI (2262.4 kcal) and EE (2172.2 kcal) than females (1930.1 kcal and 2084.5 kcal), respectively (p < 0.05). Overweight subjects had a lower EIG than did underweight and normal-weight subjects (p < 0.05). Subjects with low socioeconomic status (SES) had a lower EE (2047.0 kcal) than those with a high SES (2164.2 kcal) (p < 0.05). Conclusion: Sex and BMI were associated with EIG in adolescents from Latin America.

14.
Front Cell Infect Microbiol ; 13: 1229098, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37753486

RESUMO

Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated ß-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host's susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review.


Assuntos
Infecções Bacterianas , Imunossenescência , Humanos , Heterocromatina , Senescência Celular , Biomarcadores
15.
Clin Oral Implants Res ; 23(9): 1104-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22092788

RESUMO

OBJECTIVES: Although platelet-rich plasma (PRP) has been proposed as a therapeutic tool to enhance wound repair, the cellular and molecular mechanisms stimulated by this agent are still not completely understood. The present study was designed to characterize the effects of PRP and platelet-poor plasma (PPP) supernatants on cell responses involved in gingival tissue repair. METHODS: We studied the response of human gingival fibroblasts (HGF) to PRP and PPP fractions on: matrix contraction, cell migration, myofibroblastic differentiation, production of matrix components and proteolytic enzymes. PRP and PPP were obtained from donors using a commercial kit. Matrix contraction was evaluated by means of collagen lattices in the presence of matrix metalloproteinase (MMP) and actin polymerization inhibitors. The production of matrix molecules and proteinases was assessed through Western-blot. RhoA activity was evaluated through a pull-down assay. Actin distribution and focal adhesions were assessed through immunofluorescence. Transforming growth factor-beta (TGF-ß) was quantified through ELISA. RESULTS: Both PRP and PPP stimulated human gingival fibroblasts-populated collagen gel contraction and Ilomastat and cytochalasin D inhibited this response. PRP and PPP also stimulated MT1-MMP and TIMP-2 production, RhoA activation and actin cytoskeleton remodeling, cell migration/invasion and myofibroblastic differentiation. TGF-ß1 was found at significantly higher concentrations in PRP than in PPP. CONCLUSIONS: Both PRP and PPP promote wound tissue remodeling and contraction through the stimulation of actin remodeling, the activity of MMPs, promotion of cell migration, and myofibroblastic differentiation. The similar biological responses induced by PRP and PPP suggest that both platelet-derived fractions may exert a positive effect on gingival repair.


Assuntos
Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacos , Plasma Rico em Plaquetas/fisiologia , Cicatrização/efeitos dos fármacos , Actinas/análise , Adulto , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Citocalasina D/farmacologia , Ensaio de Imunoadsorção Enzimática , Humanos , Ácidos Hidroxâmicos , Indóis/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/análise , Masculino , Metaloproteinases da Matriz/farmacologia , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta/análise
16.
Front Immunol ; 13: 1044334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341447

RESUMO

Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses associated with wound healing, such as collagen synthesis, cell migration, proliferation, and collagen contraction, have been shown to be lower in gingival fibroblasts (the most abundant cells from the connective gingival tissue) in aged donors than young donors. Cellular senescence is one of the hallmarks of aging, which is characterized by the acquisition of a senescence-associated secretory phenotype that is characterized by the release of pro-inflammatory cytokines, chemokines, growth factors, and proteases which have been implicated in the recruitment of immune cells such as neutrophils, T cells and monocytes. Moreover, during aging, macrophages show altered acquisition of functional phenotypes in response to the tissue microenvironment. Thus, inflammatory and resolution macrophage-mediated processes are impaired, impacting the progression of periodontal disease. Interestingly, salivary antimicrobial peptides, such as histatins, which are involved in various functions, such as antifungal, bactericidal, enamel-protecting, angiogenesis, and re-epithelization, have been shown to fluctuate with aging. Several studies have associated the presence of Porphyromonas gingivalis, a key pathogen related to periodontitis and apical periodontitis, with the progression of Alzheimer's disease, as well as gut, esophageal, and gastric cancers. Moreover, herpes simplex virus types 1 and 2 have been associated with the severity of periodontal disease, cardiovascular complications, and nervous system-related pathologies. This review encompasses the effects of aging on periodontal tissues, how P. gingivalis and HSV infections could favor periodontitis and their relationship with other pathologies.


Assuntos
Doenças Periodontais , Periodontite , Humanos , Gengiva/patologia , Porphyromonas gingivalis , Periodonto , Doenças Periodontais/metabolismo
17.
Front Med (Lausanne) ; 9: 826218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372407

RESUMO

Purpose: Endothelial damage and angiogenesis are fundamental elements of neovascularisation and fibrosis observed in patients with coronavirus disease 2019 (COVID-19). Here, we aimed to evaluate whether early endothelial and angiogenic biomarkers detection predicts mortality and major cardiovascular events in patients with COVID-19 requiring respiratory support. Methods: Changes in serum syndecan-1, thrombomodulin, and angiogenic factor concentrations were analysed during the first 24 h and 10 days after COVID-19 hospitalisation in patients with high-flow nasal oxygen or mechanical ventilation. Also, we performed an exploratory evaluation of the endothelial migration process induced by COVID-19 in the patients' serum using an endothelial cell culture model. Results: In 43 patients, mean syndecan-1 concentration was 40.96 ± 106.9 ng/mL with a 33.9% increase (49.96 ± 58.1 ng/mL) at day 10. Both increases were significant compared to healthy controls (Kruskal-Wallis p < 0.0001). We observed an increase in thrombomodulin, Angiopoietin-2, human vascular endothelial growth factor (VEGF), and human hepatocyte growth factor (HGF) concentrations during the first 24 h, with a decrease in human tissue inhibitor of metalloproteinases-2 (TIMP-2) that remained after 10 days. An increase in human Interleukin-8 (IL-8) on the 10th day accompanied by high HGF was also noted. The incidence of myocardial injury and pulmonary thromboembolism was 55.8 and 20%, respectively. The incidence of in-hospital deaths was 16.3%. Biomarkers showed differences in severity of COVID-19. Syndecan-1, human platelet-derived growth factor (PDGF), VEGF, and Ang-2 predicted mortality. A multiple logistic regression model with TIMP-2 and PDGF had positive and negative predictive powers of 80.9 and 70%, respectively, for mortality. None of the biomarkers predicted myocardial injury or pulmonary thromboembolism. A proteome profiler array found changes in concentration in a large number of biomarkers of angiogenesis and chemoattractants. Finally, the serum samples from COVID-19 patients increased cell migration compared to that from healthy individuals. Conclusion: We observed that early endothelial and angiogenic biomarkers predicted mortality in patients with COVID-19. Chemoattractants from patients with COVID-19 increase the migration of endothelial cells. Trials are needed for confirmation, as this poses a therapeutic target for SARS-CoV-2.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35162152

RESUMO

Overweight and obesity are often explained by an imbalance between energy intake and expenditure. This, in addition to metabolic effects, makes it difficult to assess the real state of individual energy balance. This study aims to analyze the energy gaps between intake and expenditure in the adult population of Latin America, as well as its relationships with sociodemographic variables and nutrition status, to draw an epidemiological perspective based on the trends observed. The energy imbalance gap was used to this end. The difference between energy intake and expenditure can be applied as a reference to explain whether weight equilibrium can prevent weight gain. Moreover, the energy imbalance gap allows for a better understanding of the design of public health policies. Using data from the Latin American Study of Nutrition and Health, the energy imbalance gap in adult population from eight Latin-American countries was assessed in 5994 subjects aged from 19-65. Usual dietary intake was measured using two non-consecutive 24 h dietary recalls. The sociodemographic questionnaire was supplemented by anthropometric measurements. Physical activity was measured through the long International Physical Activity Questionnaire. Energy expenditure was obtained using the basal metabolic rate. For the overall sample, the mean energy intake was 1939.1 kcal (95% CI: 1926.9; 1951.3), the mean of energy expenditure was 1915.7 kcal (95% CI: 1906.4; 1924.9), and the mean of energy imbalance gap was 23.4 kcal (95% CI: 11.9; 35.0). Results show that energy intake and expenditure were higher in men. Moreover, subjects aged 19-34, of high socioeconomic level, who completed high school, were mestizos and were of normal weight consumed the highest number of calories. Overall, a positive energy imbalance gap was observed. Overweight and obese from Argentina, Costa Rica, Ecuador, Peru, and Venezuela showed a significantly lower energy imbalance gap than underweight subjects. These findings confirm the high variability of energy imbalance gap and the accompanying correlates of energy intake and expenditure. Further research is needed to specifically address interventions in low and middle-income countries such as many in Latin America, to help reduce the prevalence of obesity and eradicate undernutrition.


Assuntos
Ingestão de Energia , Estado Nutricional , Adulto , Idoso , Estudos Transversais , Metabolismo Energético , Humanos , América Latina/epidemiologia , Estilo de Vida , Masculino , Adulto Jovem
19.
Front Oncol ; 11: 621614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178620

RESUMO

Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have been achieved with drugs such as tamoxifen and trastuzumab, breast cancer still caused 627,000 deaths in 2018. Since cancer is a multifactorial disease, it has become necessary to develop new molecular therapies that can target several relevant cellular processes at once. Ion channels are versatile regulators of several physiological- and pathophysiological-related mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. Ion channels are the main regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein-protein interactions one of their main regulatory mechanisms. Among the different ion channel families, the Transient Receptor Potential (TRP) family stands out in the context of breast cancer since several members have been proposed as prognostic markers in this pathology. However, only a few approaches exist to block their specific activity during tumoral progress. In this article, we describe several TRP channels that have been involved in breast cancer progress with a particular focus on their binding partners that have also been described as drivers of breast cancer progression. Here, we propose disrupting these interactions as attractive and potential new therapeutic targets for treating this neoplastic disease.

20.
Front Mol Biosci ; 8: 701477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277709

RESUMO

Mass spectrometry-based proteomics methods are widely used to identify and quantify protein complexes involved in diverse biological processes. Specifically, tandem mass spectrometry methods represent an accurate and sensitive strategy for identifying protein-protein interactions. However, most of these approaches provide only lists of peptide fragments associated with a target protein, without performing further analyses to discriminate physical or functional protein-protein interactions. Here, we present the PPI-MASS web server, which provides an interactive analytics platform to identify protein-protein interactions with pharmacological potential by filtering a large protein set according to different biological features. Starting from a list of proteins detected by MS-based methods, PPI-MASS integrates an automatized pipeline to obtain information of each protein from freely accessible databases. The collected data include protein sequence, functional and structural properties, associated pathologies and drugs, as well as location and expression in human tissues. Based on this information, users can manipulate different filters in the web platform to identify candidate proteins to establish physical contacts with a target protein. Thus, our server offers a simple but powerful tool to detect novel protein-protein interactions, avoiding tedious and time-consuming data postprocessing. To test the web server, we employed the interactome of the TRPM4 and TMPRSS11a proteins as a use case. From these data, protein-protein interactions were identified, which have been validated through biochemical and bioinformatic studies. Accordingly, our web platform provides a comprehensive and complementary tool for identifying protein-protein complexes assisting the future design of associated therapies.

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