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OBJECTIVES: Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is a disease characterized by chronic inflammation and tissue remodeling process. The remodeling process in nasal polyps has mainly been studied by histology analysis. However, it is limited to a polyp fragment and requires tissue removal. The present study aims to evaluate the ability of Magnetic Resonance Imaging (MRI) to depict and characterize the remodeling process in patients with CRSwNP. METHODS: 30 patients that met clinical diagnostic criteria for CRSwNP, without previous history of rhinosinusitis surgery were submitted to MRI scan (conventional, diffusion-weighted and DCE MRI) and compared with polyp tissue histological findings, IL-6 concentrations in the tissue and eosinophil count in the blood. The examinations were evaluated, independently, by two radiologists blinded to other radiological and histological data. The pathologist, blinded to MRI results, also compared the tissue sample from the most central and the most peripheral portion of the polypoid tissue adjacent to the floor of the nasal fossa. RESULTS: This study demonstrated a characteristic pattern of nasal polyps, whose peripheral portions of nasal polypoid tissue are edematous, whereas the central portions in the middle meatus and in the middle and upper ethmoid are predominantly fibrotic. ADC values found in the most anterior portion of the polyps may be a marker for radiological phenotyping the remodeling process. This non-invasive analysis presented a high degree of agreement in the fibrosis and edema rating by two radiologists and the histological analysis was concordant with the MRI findings. The polyps were characterized as eosinophilic, and no relationship was found between the severity of the eosinophilic inflammatory process or concentration of IL-6 and the remodeling process. CONCLUSION: MRI by using T2-weighted imaging sequence and ADCs values allows tissue characterization and is an effective tool for the differentiation of edematous and fibrotic components in CRSwNP.
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Neutrophilic asthma is generally defined by poorly controlled symptoms and high levels of neutrophils in the lungs. Short-chain fatty acids (SCFAs) are proposed as nonpharmacological therapy for allergic asthma, but their impact on the neutrophilic asthma lacks evidence. SCFAs regulate immune cell responses and impact the inflammasome NLRP3, a potential pharmacological target for neutrophilic asthma. Here, we explored the capacity of SCFAs to mitigate murine-induced neutrophilic asthma and the contribution of NLRP3 to this asthma. The objective of this study is to analyze whether SCFAs can attenuate lung inflammation and tissue remodeling in murine neutrophilic asthma and NLRP3 contribution to this endotype. Wild-type (WT) C57BL6 mice orotracheally received 10 µg of HDM (house dust mite) in 80 µL of saline on days 0, 6-10. To explore SCFAs, each HDM group received 200 mM acetate, propionate, or butyrate. To explore NLRP3, Nlrp3 KO mice received the same protocol of HDM. On the 14th day, after euthanasia, bronchoalveolar lavage fluid (BALF) and lungs were collected to evaluate cellularity, inflammatory cytokines, and tissue remodeling. HDM group had increased BALF neutrophil influx, TNF-α, IFN-γ, IL-17A, collagen deposition, and mucus secretion compared to control. SCFAs distinctively attenuate lung inflammation. Only features of tissue remodeling were Nlrp3-dependent such as collagen deposition, mucus secretion, active TGF-ß cytokine, and IMs CD206+. SCFAs greatly decreased inflammatory cytokines and tissue remodeling. Only tissue remodeling was dependent on NLRP3. It reveals the potential of SCFAs to act as an additional therapy to mitigate neutrophilic asthma and the NLRP3 contribution to asthma.
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Asma , Ácidos Graxos Voláteis , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neutrófilos , Pneumonia , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Asma/metabolismo , Asma/imunologia , Asma/tratamento farmacológico , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Pneumonia/metabolismo , Pneumonia/imunologia , Camundongos Knockout , Pyroglyphidae/imunologia , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Citocinas/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/químicaRESUMO
Brown and beige adipose tissue share similar functionality, being both tissues specialized in producing heat through nonshivering thermogenesis and also playing endocrine roles through the release of their secretion factors called batokines. This review elucidates the influence of physical exercise, and myokines released in response, on the regulation of thermogenic and secretory functions of these adipose tissues and discusses the similarity of batokines actions with physical exercise in the remodeling of adipose tissue. This adipose tissue remodeling promoted by autocrine and paracrine batokines or physical exercise seems to optimize its functionality associated with better health outcomes.
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Tecido Adiposo Bege , Tecido Adiposo Marrom , Humanos , Termogênese/fisiologia , Obesidade , Exercício FísicoRESUMO
In cancer associated cachexia (CAC), white adipose tissue undergoes morphofunctional and inflammatory changes that lead to tissue dysfunction and remodeling. In addition to metabolic changes in white adipose tissues (WAT), adipose tissue atrophy has been implicated in several clinical complications and poor prognoses associated with cachexia. Adipocyte atrophy may be associated with increased beige remodeling in human CAC as evidenced by the "beige remodeling" observed in preclinical models of CAC. Even though beige remodeling is associated with CAC-induced WAT dysfunction, there are still some open questions regarding their cellular origins. In this study, we investigated the development of beige remodeling in CAC from a broader perspective. In addition, we used a grading system to identify the scAT as being affected by mice weight loss early and intensely. Using different in vitro and ex-vivo techniques, we demonstrated that Lewis LLC1 cells can induce a switch from white to beige adipocytes, which is specific to this type of tumor cell. During the more advanced stages of CAC, beige adipocytes are mainly formed from the transdifferentiation of cells. According to our results, humanizing the CAC classification system is an efficient approach to defining the onset of the syndrome in a more homogeneous manner. Pathological beige remodeling occurred early in the disease course and exhibited phenotypic characteristics specific to LLC cells' secretomes. Developing therapeutic strategies that recruit beige adipocytes in vivo may be better guided by an understanding of the cellular origins of beige adipocytes emitted by CAC.
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Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.
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Extracellular matrix (ECM) proteins in the mammary gland provide structure and regulate its development and homeostasis. Alterations in its structure can regulate and support pathogenesis, like breast tumors. Aiming to identify the health and tumoral canine mammary ECM scaffold protein profile by immunohistochemistry, the decellularization process was carried out to remove the cellular content. Additionally, it was verified the influence of health and tumoral ECM on the attachment of health and tumoral cells. The types I, III, IV, and V structural collagens were scarce in the mammary tumor, and ECM fibers were disorganized. Vimentin and CD44 were more common in mammary tumor stroma, suggesting a role in cell migration that results in tumor progression. Elastin, fibronectin, laminin, vitronectin, and osteopontin were similarly detected under healthy and tumor conditions, providing the attachment of normal cells in healthy ECM, while tumoral cells were able to attach in tumoral ECM. The protein pattern demonstrates ECM alteration in canine mammary tumorigenesis, presenting new knowledge on mammary tumor ECM microenvironment.
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Proteínas da Matriz Extracelular , Neoplasias , Animais , Cães , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Laminina , Tecido Conjuntivo , Neoplasias/patologia , Microambiente TumoralRESUMO
OBJECTIVE: Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. METHODS: Samples were streamed as early Nasal Polyps (eNP, n=10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n=14), and Control group (n=15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-ß1 (Transforming Growth Factor-beta 1) activator, TGF-ß1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. RESULTS: The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-ß1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-ß1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-ß1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. CONCLUSION: Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-ß1-mediated PAI-1 reduction. LEVEL OF EVIDENCE: 3b.
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Pólipos Nasais , Fator de Crescimento Transformador beta1 , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Given obesity and its associated metabolic disorders have reached epidemic proportions, the study of therapeutic strategies targeting white adipose tissue (WAT) are of main research interest. We previously shown that α-linolenic acid-rich chia seed was able to ameliorate a wide range of metabolic disorders including body fat accretion in sucrose-rich diet (SRD)-fed rats, an experimental model of visceral adiposity and insulin resistance. However, the mechanisms involved are not fully clarified. The aim of this study was to evaluate the effect of chia seed administration upon WAT remodeling and key enzymes that controls lipolysis, insulin signaling (tAKT, pAKT), and GLUT-4 levels in different visceral fat pad depots (epididymal -eWAT- and retroperitoneal -rWAT- adipose tissues) of SRD-fed rats. Results showed that chia seed reduces adipocytes hypertrophy, the increased lipid content and collagen deposition in both WAT. These changes were accompanied by a significant reduction of HSL and ATGL protein levels in eWAT and HSL protein levels in rWAT. Moreover, chia seed restored the altered expression pattern of the pAKT observed in SRD-fed rats, and modulated GLUT-4 levels. Chia seed could be a dietary intervention of great relevance with potential beneficial effects in the management of body fat excess and WAT function.
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Salvia , Ácido alfa-Linolênico , Adiposidade , Animais , Colágeno , Dieta , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Extratos Vegetais , Ratos , Ratos Wistar , Roedores/metabolismo , Salvia/metabolismo , Salvia hispanica , Ácido alfa-Linolênico/farmacologiaRESUMO
BACKGROUND: The prostate is susceptible to changes in androgen levels, which can play an important role in the development of Benign Prostatic Hyperplasia (BPH). Natural compounds have beneficial properties for organisms and can be an important therapeutic strategy in the treatment of diseases. ß-Caryophyllene (BCP) is a phytocannabinoid present in several medicinal and food plants species and has shown beneficial effects in different organs. However, little is known about its effects on the prostate. The present study seeks to evaluate the effects of exposure to BCP on the morphophysiology of the ventral prostate of adult gerbils supplemented with testosterone. METHODS: Animals were distributed into four groups (n = 8/group): Intact control (C); ß-Caryophyllene (BCP): ß-Caryophyllene (50 mg/kg/day); Testosterone (T): animals received subcutaneous injections of Testosterone Cypionate (3 mg/Kg), on alternate days, for one month and were euthanized 30 days supplementation ended; Testosterone and ß-Caryophyllene (TBCP): animals were exposed to testosterone cypionate (3 mg/Kg) to induce hyperplastic alterations followed by daily BCP (50 mg/kg). Morphological, biometric, immunohistochemical, and serological analyses were performed. RESULTS: Proliferative disorders and inflammatory foci were present in the ventral prostate of all experimental groups. An increase in the multiplicity of benign intraepithelial neoplasm and subepithelial inflammatory foci was observed in T group. The incidence of intraluminal inflammatory foci and microinvasive carcinoma was verified only in the T group. Cellular rearrangement and tissue remodeling occurred in the prostate of groups exposed to phytocannabinoids. A reduction was observed in the frequency of PHH3 and Cox2 markers in the prostatic epithelium of TBCP in comparison with T. A decrease in F4/80 and CD163 positive macrophages were also observed in the prostatic stroma of the TBCP group in comparison with T. The results suggest that BCP had favorable effects on BPH, reducing the proliferation and frequency of some inflammatory cells. CONCLUSION: BCP impacts the tissue remodeling process in the premalignant prostate environment and that the use of this phytocannabinoid can have a promising effect in the handling of BPH.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Sesquiterpenos Policíclicos/administração & dosagem , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Animais , Proliferação de Células/fisiologia , Gerbillinae , Injeções Subcutâneas , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Testosterona/administração & dosagem , Testosterona/análogos & derivados , Testosterona/toxicidade , Resultado do TratamentoRESUMO
AIMS: Although excessive fat and caffeine intake are independent risk factors for bone microstructural and functional disturbances, their association remains overlooked. Thus, we investigated the impact of high-fat diet (HFD) and caffeine alone and combined on serum lipid profile, bone microstructure, micromineral distribution and biomechanical properties. METHODS: Forty female C57BL/6 mice were randomized into 4 groups daily treated for seventeen weeks with standard diet (SD) or HFD (cafeteria diet) alone or combined with 50 mg/kg caffeine. KEY FINDINGS: The association between HFD and caffeine reduced the weight gain compared to animals receiving HFD alone. Caffeine alone or combined with HFD increases total and HDL cholesterol circulating levels. HFD also reduced calcium, phosphorus and magnesium bone levels compared to the groups receiving SD, and this reduction was aggravated by caffeine coadministration. From biomechanical assays, HFD combined with caffeine increased bending strength and stiffness of tibia, a finding aligned with the marked microstructural remodeling of the cortical and cancellous bone in animals receiving this combination. SIGNIFICANCE: Our findings indicated that HFD and caffeine interact to induce metabolic changes and bone microstructural remodeling, which are potentially related to bone biomechanical adaptations in response to HFD and caffeine coadministration.
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Peso Corporal , Osso e Ossos/fisiopatologia , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Animais , Fenômenos Biomecânicos , Osso e Ossos/efeitos dos fármacos , Colesterol/sangue , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Chronic rhinosinusitis without nasal polyposis (CRSsNP) and Chronic rhinosinusitis with nasal polyposis (CRSwNP) present distinct tissue remodeling processes. The proteins involved in the process of tissue remodeling have their production and activity related to the inflammatory environment they are. This study aimed to evaluate the protein expression of BMP-7, MMP-9, TGF-ß in chronic sinusitis with and without nasal polyposis and their relations with IL-6 and IL-10. METHODS: Cross-sectional observational study with 86 participants was divided into three groups: patients with CRSwNP (n = 34), patients with CRSsNP (n = 26), and a control group (CG) without inflammatory disease of the nasal mucosa (n = 26). The primary outcomes were the concentrations of BMP-7, MMP-9, TGF-ß, IL-6, and IL-10. Secondary outcomes were the correlations of these markers. RESULTS: The TGF-ß dosage was elevated in the CRSsNP group and reduced in the CSwNP group. The dosage of IL-6 was higher in the CSwNP group, and the IL-10 dosage lower in the groups with sinusitis, and IL-10 was positively correlated with BMP-7 in all groups. There was a negative correlation between IL-6 and IL-10 in all groups observed. The correlation between MMP-9 and interleukins was lost in the CRSsNP group. There was a positive correlation between TGF-ß and IL-6 in the CG, and negative in the CRSsNP group. CONCLUSION: An inflammation shown in rhinosinusitis with an increase in IL-6 and decrease in IL-10 when compared with the control group; only TGF-ß was altered in the tissue remodeling process when compared with BMP-7 and MMP-9 in rhinosinusitis. There is a loss of correlation between tissue remodeling proteins and interleukins studied in CRSsNP.
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Pólipos Nasais , Rinite , Sinusite , Proteína Morfogenética Óssea 7 , Doença Crônica , Estudos Transversais , Humanos , Interleucina-10 , Interleucina-6 , Metaloproteinase 9 da Matriz , Mucosa Nasal , Pólipos Nasais/complicações , Rinite/complicações , Sinusite/complicações , Fator de Crescimento Transformador betaRESUMO
Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.
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Antiulcerosos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Flavonoides/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ácido Acético/toxicidade , Animais , Antiulcerosos/farmacologia , Apoptose/genética , Caspase 3/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Etanol/toxicidade , Flavonoides/farmacocinética , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Inflamação , Interleucina-10/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/enzimologiaRESUMO
Appropriate remodeling of the female lower reproductive tract and pelvic floor is essential during normal mammalian pregnancy, labor, and postpartum recovery. During mouse pregnancy, in addition to reproductive tract modifications, the pubic symphysis (PS) is remodeled into a soft interpubic ligament (IpL) to provide safe delivery of the offspring and fast postpartum recovery. Although temporal changes in the phenotypes of myeloid cells, such as mononuclear phagocytes, are crucial to remodeling the lower reproductive tract organs in preparation for a safe delivery, little is known about the involvement of recruited monocytes or macrophages in mouse PS remodeling. We used combined light microscopy, electron microscopy, and qPCR analysis to investigate the profile of recruited monocytes and macrophage polarization markers in C57Bl6 mouse interpubic tissues during pregnancy (D12, D18, and D19) and early days postpartum (1 dpp and 3 dpp) to better identify their presence in proper remodeling of the mouse PS. Our morphological data show that the number of recruited monocytes is increased in interpubic tissues and that recruited monocytes differentiate into proinflammatory or anti-inflammatory macrophage phenotypes from D18 to 3 dpp, which may contribute to dynamic changes in the gene expression of specific inflammatory mediators involved in interpubic tissue remodeling at these time points. Therefore, our morphological and quantitative gene expression data suggest that both differentiated macrophages from recruited monocytes and polarized macrophages may collaborate for IpL relaxation at labor and the appropriate repair of the PS after the first pregnancy.
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Macrófagos/fisiologia , Monócitos/fisiologia , Período Pós-Parto/fisiologia , Sínfise Pubiana/fisiologia , Animais , Feminino , Ligamentos/citologia , Camundongos , GravidezRESUMO
Physical training (PT) has been considered as a treatment in metabolic syndrome (MS), since it induces thermogenic activity in brown (BAT) and white (WAT) adipose tissues. We evaluated the therapeutic effect of PT on activity of WAT and BAT in rats with MS induced by high-fat diet (30% lard) for 13 weeks and submitted, for the last 6 weeks, to swimming or kept sedentary (SED) rats. MS-SED rats compared to control diet (CT-SED) rats showed low physical fitness and high levels of glucose, insulin, homeostasis evaluation of insulin resistance (HOMA-IR), homeostasis evaluation of the functional capacity of ß-cells (HOMA-ß), and blood pressure. The gastrocnemius muscle decreased in peroxisome proliferator-activated receptor gamma coactivator 1-alpha and beta (PGC-1α, PGC-1ß), and uncoupled protein 2 and 3 (UCP2 and UCP3) expressions. Both WAT and BAT increased in the adipocyte area and decreased in blood vessels and fibroblast numbers. WAT increased in expression of pro-inflammatory adipokines and decreased in anti-inflammatory adipokine and adiponectin. WAT and gastrocnemius showed impairment in the insulin signaling pathway. In response to PT, MS rats showed increased physical fitness and restoration of certain biometric and biochemical parameters and blood pressure. PT also induced thermogenic modulations in skeletal muscle, WAT and BAT, and also improved the insulin signaling pathway. Collectively, PT was effective in treating MS by inducing improvement in physical fitness and interchangeable effects between skeletal muscle, WAT and BAT, suggesting a development of brown-like adipocyte cells.
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Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Adiposidade , Resistência à Insulina , Síndrome Metabólica/terapia , Condicionamento Físico Animal , Termogênese , Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo Marrom/irrigação sanguínea , Tecido Adiposo Marrom/imunologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/irrigação sanguínea , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Animais , Biomarcadores/sangue , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Regulação da Expressão Gênica , Hiperglicemia/etiologia , Hiperglicemia/prevenção & controle , Hiperinsulinismo/etiologia , Hiperinsulinismo/prevenção & controle , Hipertensão/etiologia , Hipertensão/prevenção & controle , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Distribuição Aleatória , Ratos Endogâmicos F344 , DesmameRESUMO
The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice.
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Terapia com Luz de Baixa Intensidade , Pele/citologia , Pele/efeitos da radiação , Engenharia Tecidual/métodos , Colágeno/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Pele/metabolismo , Sobrevivência de Tecidos/efeitos da radiação , Cicatrização/efeitos da radiaçãoRESUMO
Recurrent pregnancy loss (RPL) is a reproductive disorder defined as two or more successive and spontaneous pregnancy losses (before 20 weeks of gestation), which affects approximately 1-2% of couples. At present, the causes of RPL remain unknown in a considerable number of cases, leading to complications in treatment and high levels of stress in couples. Idiopathic recurrent pregnancy loss (iRPL) has become one of the more complicated reproductive problems worldwide due to the lack of information about its etiology, which limits the counseling and treatment of patients. For that reason, iRPL requires further study of novel factors to provide scientific information for determining clinical prevention and targeted strategies. The aim of this study is to describe the most recent and promising progress in the identification of potential genetic and epigenetic risk factors for iRPL, expanding the genetic etiology of the disease.
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Aborto Habitual/genética , Epigênese Genética , Tolerância Imunológica/genética , Aberrações Cromossômicas , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Gravidez , Telômero , Trombofilia/genéticaRESUMO
Angiogenesis in inflammation are hallmarks for adipose tissue expansion in obesity. The role of angiopoietin/Tie-2 system in adipose tissue expansion and immune cell recruitment is unclear. We studied the effect of sleeve gastrectomy and the influence of FTO rs9930506 polymorphism on Tie-2, angiopoietin-1 and angiopoietin-2 expression in morbid obesity. Fifteen morbidly obese subjects (4 men and 11 women) aged 24-55 years were followed-up 3 and 6 months after sleeve gastrectomy. Serum sTie-2, angiopoietin-1, angiopoietin-2, and hypoxia-inducible factor-1α concentrations were determined by ELISA. Tie-2 and its ligands in visceral and subcutaneous adipose tissue were localized by immunohistochemistry. Tie-2 expression was measured by flow cytometry in circulating monocytes and infiltrated macrophages. Comparisons before and after sleeve gastrectomy were carried out using ANOVA for repeated measures. rs9930506FTO genotyping was performed by PCR-RFLP. Circulating sTie-2 and angiopoietin-2 were higher before sleeve gastrectomy. Tie-2 and angiopoietin-2 mRNA levels were higher in subcutaneous adipose tissue than visceral and both decreased after surgery. Monocytes and infiltrated macrophages showed a pro-inflammatory phenotype, with increased Tie-2 expression that decreased 3 and 6 months after sleeve gastrectomy. Baseline sTie-2 correlated inversely with adiponectin levels. At baseline the rs9930506FTO AG ó GG genotypes carriers had more 34 kg than genotype carriers of rs9930506 AA. Weight and body mass index decreased at 6 months. We found that angiopoietin/Tie-2 system is mainly expressed in subcutaneous adipose tissue, contributing to expandability, fat accumulation, and monocytes attachment in obesity. Bariatric surgery favorably modifies the pro-angiogenic profile, allowed a reduced angiogenic expression in the circulation and adipose tissue.
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Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Angiopoietinas/metabolismo , Gastrectomia , Obesidade Mórbida/metabolismo , Receptor TIE-2/metabolismo , Adulto , Antropometria , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/imunologia , Obesidade Mórbida/cirurgia , Polimorfismo de Nucleotídeo Único , Gordura Subcutânea/imunologia , Gordura Subcutânea/metabolismo , Adulto JovemRESUMO
The spleen is one of the major immunological sites for maintaining blood homeostasis. Previous studies showed that heterogeneous splenic macrophage populations contribute in complimentary ways to control blood-borne infections and induce effective immune responses. Marginal metallophilic macrophages (MMMΦs) and marginal zone macrophages (MZMΦs) are cells with great ability to internalize blood-borne pathogens such as virus or bacteria. Their localization adjacent to T- and B-cell-rich splenic areas favors the rapid contact between these macrophages and cells from adaptive immunity. Indeed, MMMΦs and MZMΦs are considered important bridges between innate and adaptive immunity. Although red pulp macrophages (RpMΦs) are mainly considered scavengers for senescent erythrocytes, several data indicate a role for RpMΦs in control of infections such as blood-stage malaria as well as in the induction of innate and adaptive immunity. Here, we review current data on how different macrophage subsets recognize and help eliminate blood-borne pathogens, and, in turn, how the inflammatory microenvironment in different phases of infection (acute, chronic, and after pathogen clearance) influences macrophage function and survival.
RESUMO
The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling.
Assuntos
Angiotensina II/metabolismo , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/fisiologia , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Hipertensão/fisiopatologia , Nefropatias/fisiopatologia , Camundongos , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/metabolismo , Proto-Oncogene Mas , RatosRESUMO
A doença venosa crônica (DVC) é uma desordem complexa que compreende sinais e sintomas que variam das telangiectasias às úlceras ativas. A DVC é classificada de acordo com aspectos clínicos, etiológicos, anatômicos e fisiopatológicos (CEAP) em sete classes variando de C0 à C6. A principal causa da DVC é a hipertensão venosa que altera o fluxo venoso e, consequentemente, a força de cisalhamento que induz alterações fenotípicas nas células endoteliais que passam a expressar mediadores pró-inflamatórios e pró-trombóticos, que levam à adesão de leucócitos, ao aumento do estresse oxidativo, da permeabilidade vascular e do dano endotelial e ao remodelamento tecidual e vascular.Em virtude dos inúmeros mecanismos e da diversidade de moléculas envolvidas na patogênese e progressão da DVC, é essencial conhecer a interação entre elas e também saber quais são as moléculas (biomarcadores) que se correlacionam positivamente ou negativamente com a gravidade da doença. Foram avaliados os níveis de Interleucina-6 (IL-6), sL-selectina, sE-selectina, sP-selectina, molécula de adesão intercelular-1solúvel (sICAM-1), molécula de adesão das células vasculares-1 solúvel (sVCAM-1), ativador tecidual do plasminogênio (tPA), atividade do inibidor do ativador do plasminogênio-1 (PAI-1), trombomodulina solúvel (sTM), fator de von Willebrand (vWF), metaloproteinase de matriz (MMP)-2, MMP-3, MMP-9, inibidor tecidual das MMPs -1 (TIMP-1), angiopoietina-1 e -2, sTie-2 e s-Endoglina e fator de crescimento do endotélio vascular (VEGF) no sangue coletado da veia braquial de 173 mulheres com DVC primária divididas em grupos C2, C3, C4 e C4 menopausadas (C4m) e de 18 voluntárias saudáveis (grupo C0a). Foram também analisados os níveis urinários de ent-prostaglandina F2α nesses grupos. Não foram encontradas diferenças estatisticamente significativas com relação às concentrações sanguíneas e urinárias de sE-selectina, sP-selectina, sICAM-1, atividade de PAI-1, MMP-3, razão TIMP-1/MMP-3 ...
Chronic Venous Disease (CVD) is a complex disorder, which encompasses signs and symptoms that vary from telangiectasias to active ulcers. The CVD is classified according Clinical, Etiologic, Anatomical and Pathophysiological (CEAP) aspects into seven classes varying from C0 to C6. The main cause of CVD is venous hypertension, which alters venous flow and consequently, shear stress. Abnormal shear stress induces phenotypic changes in endothelial cells that start to express pro-inflammatory and pro-thrombotic mediators that lead to leukocyte adhesion, oxidative stress, increased vascular permeability and endothelial cell damage and tissue and vascular remodeling. Due to several mechanisms and the diversity of molecules involved in the pathogenesis and progression of CVD, is essential to know the interplay between them and which are the molecules (biomarkers) that correlate positively and negatively with the severity of the disease. We investigated the levels of interleukin-6 (IL-6), sL-selectin, sE-selectin, sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, soluble thrombomodulin (sTM), von Willebrand factor (vWf), matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metaloproteinases-1 (TIMP-1), angiopoietin-1 and -2, sTie-2, s-Endoglin, vascular endothelial growth factor (VEGF) in the blood taken from the brachial vein of 173 patients with primary CVD divided into C2, C3, C4 and menopaused C4 (C4m) groups and 18 healthy volunteers (C0a group).We also investigated the urinary levels of ent-prostaglandin F2α in these groups. There was no statistically significant difference between groups with respect to blood or urinary levels of sE-selectin, sP-selectin, sICAM-1, PAI-1 activity, MMP-3, TIMP-1/MMP-3 ratio, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, s-Endoglin ...