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1.
Mol Immunol ; 124: 109-116, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32554101

RESUMO

Disordered collagen production by fibroblasts in response to tissue injury contributes to pulmonary fibrosis (PF). Therefore, elimination of collagen deposition has becoming a potential target in PF treatment which despite standard anti-fibrosis regiment still remains challenge. Curcumin and curcumol are regarded as the main active components extraction from the rhizomes of Curcuma zedoaria, which is widely used for inhibition the proliferation of multiple cells. However, the molecular basis for the function of curcumin and curcumol in limiting fibrogenesis still unknown. In this study, we have investigated the effects of curcumin and curcumol in the fibroblast overproliferation model human lung fibroblast (HLF) inducing by TGF-ß1. The growth-inhibitory effects of the components wasn't observed from 8 to 64 µg/ml. Administration of curcumin or curcumol significantly diminished the level of hydroxyproline hydroxyproline and α-smooth muscle actin (α-SMA), also the collagen Ⅰ (Col-Ⅰ) and collagen Ⅲ (Col-Ⅲ) deposition were reduced in the HLF. Furthermore, related to the collagen synthesis proteins including N-terminal pro-peptide for Type Ⅰ collagen (PⅠNP), N-terminal pro-peptide for Type Ⅲ collagen (PⅢNP) and prolyl-hydroxylase (PHD) were degraded gracefully at dose-dependent manner. Autophagy as the scavenger was crippled in TGF-ß1-fibroblast overproliferation HLF, conversely the increased autophagosomes have been spotted in cytoplasm under transmission electron microscope which is consistent with up-regulation of Beclin1 and ATG7 after treatment with curcumin or curcumol in this study. Additionally, blocking autophagy by inhibitor chloroquine (CQ) caused collagen deposition, providing further evidence regard to autophagy activation capacity of curcumin and curcumol. Our findings provide a detailed understanding that the function of curcumin and curcumol on decreasing collagen deposition mediating by autophagy mechanism, which may also inspire the further research on PF at different perspectives.


Assuntos
Autofagia/efeitos dos fármacos , Colágeno/efeitos dos fármacos , Curcumina/farmacologia , Fibroblastos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células Cultivadas , Curcuma , Humanos , Extratos Vegetais/farmacologia , Fibrose Pulmonar/patologia
2.
Int. j. morphol ; 38(3): 755-760, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098316

RESUMO

SUMMARY: The objective of this study was to describe the effects of monosodium glutamate on the collagen of the parotid gland in an obesity model. 18 newborn male Sprague Dawley rats were used (first control group; second group of MSG1: 4 mg/g of monosodium glutamate weight, 5 doses, and third group of MSG2: 4 mg/g of monosodium glutamate, 5 doses, maintained for 8 and 16 weeks respectively). The content and type of collagen were analyzed, in addition to the levels of cholesterol, glucose, triglycerides and uric acid. Monosodium glutamate produced an increase in the obesity rates of the MSG2 group, in addition to an increase in blood cholesterol, glucose and uric acid levels compared to the control group. Type III collagen in the MSG2 group showed a statistically significant increase. Monosodium glutamate induced obesity, in addition to an increase in type III collagen fibers.


RESUMEN: El objetivo de este estudio fue describir los efectos del glutamato monosódico sobre el colágeno de la glándula parótida en un modelo de obesidad. Se utilizaron 18 ratas Sprague Dawley machos recién nacidas (primer grupo control; segundo grupo MSG1: 4 mg/g de peso de glutamato monosódico, 5 dosis, y tercer grupo MSG2: 4 mg/g de glutamato monosódico, 5 dosis, mantenidas durante 8 y 16 semanas respectivamente). Se analizó el contenido y el tipo de colágeno, además de los niveles de colesterol, glucosa, triglicéridos y ácido úrico. El glutamato monosódico produjo un aumento en las tasas de obesidad del grupo MSG2, además de un aumento en los niveles de colesterol en sangre, glucosa y ácido úrico en comparación con el grupo control. El colágeno tipo III en el grupo MSG2 mostró un aumento estadísticamente significativo. La obesidad inducida por glutamato monosódico, además de un aumento en las fibras de colágeno tipo III.


Assuntos
Animais , Masculino , Ratos , Glândula Parótida , Glutamato de Sódio/toxicidade , Colágeno/efeitos dos fármacos , Obesidade/induzido quimicamente , Glândulas Salivares/efeitos dos fármacos , Triglicerídeos/sangue , Ácido Úrico/sangue , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Colágeno/análise , Ratos Sprague-Dawley , Modelos Animais de Doenças , Animais Recém-Nascidos
3.
Medicine (Baltimore) ; 99(20): e20091, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443319

RESUMO

This study aims to evaluate the changes of fragility and ultrastructure of amniotic membrane after cross-linking by UVA/riboflavin.Forty-nine fresh amniotic membranes were randomly divided into 3 groups. Eighteen were in group A (CX group) and immersed in 0.1% riboflavin solution for 10 min for UVA/riboflavin cross-linking. Sixteen were in group B (B2 group), soaked for 10 min with 0.1% riboflavin. After soaking, membranes in group A and B were transferred into corneal preservation solution. Fifteen pieces were in group C, directly into corneal preservation solution. The biomechanical and ultrastructural changes of the amniotic tissue before and after cross-linking were examined (CX group = 13, B2 group = 11, C group = 15). The amniotic membrane tissue of group A (n = 5) and B (n = 5) was transplanted into 16 eyes of the rabbits, respectively, and the dissolution time of the amniotic membrane tissue was investigated.After cross-linking, compared with the control group, the elastic modulus of the low-stress area of the amniotic membrane (Elow) was higher, while the elastic modulus of the high-stress area of the amniotic membrane (Ehigh) was lower, with no significant difference in the tensile strength. Also, the collagen fibers showed coarse and bamboo-like changes. In group A, amniotic membranes began to dissolve 4 weeks after conjunctiva transplantation, and all amniotic membranes were dissolved and absorbed 6 weeks after conjunctiva transplantation. In group B, some amniotic membrane tissues were still visible 6 weeks after conjunctiva transplantation.This study suggested that after amniotic membrane cross-linking, the brittleness was increased, the hardness was enhanced, and the morphology of the collagen fiber was changed. The cross-linked amniotic membrane showed resistance to tissue dissolution.


Assuntos
Âmnio/fisiologia , Âmnio/ultraestrutura , Reagentes para Ligações Cruzadas , Riboflavina , Transplante , Raios Ultravioleta , Implantes Absorvíveis , Âmnio/efeitos dos fármacos , Âmnio/transplante , Animais , Colágeno/efeitos dos fármacos , Colágeno/efeitos da radiação , Módulo de Elasticidade , Olho , Humanos , Procedimentos Cirúrgicos Oftalmológicos , Soluções para Preservação de Órgãos , Coelhos , Distribuição Aleatória
4.
J Surg Res ; 253: 280-287, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402853

RESUMO

BACKGROUND: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. METHODS: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH. RESULTS: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm2versus 1.4 ± 1.5 mm2, respectively, P = 0.045) and medial area (5.1 ± 1.9 mm2versus 2.7 ± 2.4 mm2, respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. CONCLUSIONS: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.


Assuntos
Artérias Carótidas/cirurgia , Neointima/prevenção & controle , Fotoquimioterapia/métodos , Veia Safena/transplante , Enxerto Vascular/métodos , Túnica Adventícia/efeitos dos fármacos , Túnica Adventícia/efeitos da radiação , Animais , Colágeno/química , Colágeno/efeitos dos fármacos , Colágeno/efeitos da radiação , Feminino , Corantes Fluorescentes/administração & dosagem , Luz , Neointima/diagnóstico , Neointima/etiologia , Neointima/patologia , Rosa Bengala/administração & dosagem , Veia Safena/diagnóstico por imagem , Veia Safena/patologia , Suínos , Porco Miniatura , Transplante Autólogo/efeitos adversos , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Enxerto Vascular/efeitos adversos , Grau de Desobstrução Vascular
5.
PLoS One ; 15(4): e0231619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294117

RESUMO

BACKGROUND: Tendinopathy is a common musculoskeletal disorder and current treatment options show limited success. Genipin is an effective collagen crosslinker with low cytotoxicity and a promising therapeutic strategy for stabilizing an intratendinous lesion. PURPOSE: This study examined the mechanical effect and delivery of intratendinous genipin injection in healthy and degenerated tendons. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine superficial digital flexor tendons were randomized into four groups: Healthy control (N = 25), healthy genipin (N = 25), degenerated control (N = 45) and degenerated genipin (N = 45). Degeneration was induced by Collagenase D injection. After 24h, degenerated tendons were subsequently injected with either 0.2ml of 80mM genipin or buffer only. 24h post-treatment, samples were cyclically loaded for 500 cycles and then ramp loaded to failure. Fluorescence and absorption assays were performed to analyze genipin crosslink distribution and estimate tissue concentration after injection. RESULTS: Compared to controls, genipin treatment increased ultimate force by 19% in degenerated tendons (median control 530 N vs. 633 N; p = 0.0078). No significant differences in mechanical properties were observed in healthy tendons, while degenerated tendons showed a significant difference in ultimate stress (+23%, p = 0.049), stiffness (+27%, p = 0.037), work to failure (+42%, p = 0.009), and relative stress relaxation (-11%, p < 0.001) after genipin injection. Fluorescence and absorption were significantly higher in genipin treated tendons compared to control groups. A higher degree of crosslinking (+45%, p < 0.001) and a more localized distribution were observed in the treated healthy compared to degenerated tendons, with higher genipin tissue concentrations in healthy (7.9 mM) than in degenerated tissue (2.3 mM). CONCLUSION: Using an ex-vivo tendinopathy model, intratendinous genipin injections recovered mechanical strength to the level of healthy tendons. Measured by genipin tissue distribution, injection is an effective method for local delivery. CLINICAL RELEVANCE: This study provides a proof of concept for the use of intratendinous genipin injection in the treatment of tendinopathy. The results demonstrate that a degenerated tendon can be mechanically augmented by a clinically viable method of local genipin delivery. This warrants further in vivo studies towards the development of a clinically applicable treatment based on genipin.


Assuntos
Adesivos/administração & dosagem , Colágeno/efeitos dos fármacos , Iridoides/administração & dosagem , Tendinopatia/tratamento farmacológico , Tendões/efeitos dos fármacos , Animais , Bovinos , Colágeno/metabolismo , Humanos , Injeções Intralesionais , Tendinopatia/patologia , Tendões/patologia , Resistência à Tração
6.
Curr Med Sci ; 40(1): 155-167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166678

RESUMO

Bone and teeth are derived from intrafibrillarly mineralized collagen fibrils as the second level of hierarchy. According to polymer-induced liquid-precursor process, using amorphous calcium phosphate precursor (ACP) is able to achieve intrafibrillar mineralization in the case of bone biomineral in vitro. Therefore, ACP precursors might be blended with any osteoconductive scaffold as a promising bone formation supplement for in-situ remineralization of collagens in bone. In this study, mesoporous silica nanoparticles with carboxyl-functionalized groups and ultra large-pores have been synthesized and used for the delivery of liquid like biomimetic precursors (ACP). The precursor delivery capacity of the nanoparticles was verified by the precursor release profile and successful mineralization of 2D and 3D collagen models. The nanoparticles could be completely degraded in 60 days and exhibited good biocompatibility as well. The successful translational strategy for biomineralization precursors showed that biomineralization precursor laden ultra large pore mesoporous silica possessed the potential as a versatile supplement in demineralized bone formation through the induction of intrafibrillar collagen mineralization.


Assuntos
Fosfatos de Cálcio/farmacologia , Colágeno/química , Células-Tronco Mesenquimais/citologia , Dióxido de Silício/química , Animais , Biomineralização/efeitos dos fármacos , Fosfatos de Cálcio/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/efeitos dos fármacos , Feminino , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas , Porosidade , Ratos
7.
Rev Col Bras Cir ; 46(6): e20192322, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32022111

RESUMO

OBJECTIVE: to evaluate the effects of arginine on abdominal wall healing in rats. METHODS: we submitted 20 Wistar rats to laparotomy and divided them into two groups, arginine and control, which then received, respectively, daily intraperitoneal treatment with arginine (300mg/kg/day) and weight-equivalent phosphate buffered solution, during five days. On the seventh postoperative day, we collected blood and scar wall samples from both groups. We evaluated serum nitrate and nitrite levels, wound evolution by tissue hydroxyproline dosages, granulation tissue formation, percentage of mature and immature collagen, myofibroblast density and angiogenesis. We used the ANOVA and the Student's t tests with p=0.05 for comparisons between groups. RESULTS: there were no significant differences between the groups studied for nitrate and nitrite (p=0.9903), tissue hydroxyproline (p=0.1315) and myofibroblast density (p=0.0511). The arginine group presented higher microvascular density (p=0.0008), higher percentage of type I collagen (p=0.0064) and improved granulation tissue formation, with better angiofibroblastic proliferation rates (p=0.0007) and wound edge reepithelization (p=0.0074). CONCLUSION: in the abdominal wall healing evaluation of Wistar rats under arginine treatment, there was no change in serum nitrate and nitrite levels, total collagen deposition and myofibroblast density. There was an increase in type I collagen maturation, microvascular density and improvement in scar granulation tissue formation by better edge reepithelization and angiofibroblastic proliferation.


Assuntos
Parede Abdominal/cirurgia , Arginina/farmacologia , Colágeno/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Traumatismos Abdominais/tratamento farmacológico , Parede Abdominal/patologia , Animais , Colágeno/metabolismo , Modelos Animais , Miofibroblastos/efeitos dos fármacos , Ratos , Ratos Wistar
8.
Nat Cell Biol ; 22(1): 74-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31907414

RESUMO

Collagen is the most abundant secreted protein in vertebrates and persists throughout life without renewal. The permanency of collagen networks contrasts with both the continued synthesis of collagen throughout adulthood and the conventional transcriptional/translational homeostatic mechanisms that replace damaged proteins with new copies. Here, we show circadian clock regulation of endoplasmic reticulum-to-plasma membrane procollagen transport by the sequential rhythmic expression of SEC61, TANGO1, PDE4D and VPS33B. The result is nocturnal procollagen synthesis and daytime collagen fibril assembly in mice. Rhythmic collagen degradation by CTSK maintains collagen homeostasis. This circadian cycle of collagen synthesis and degradation affects a pool of newly synthesized collagen, while maintaining the persistent collagen network. Disabling the circadian clock causes abnormal collagen fibrils and collagen accumulation, which are reduced in vitro by the NR1D1 and CRY1/2 agonists SR9009 and KL001, respectively. In conclusion, our study has identified a circadian clock mechanism of protein homeostasis wherein a sacrificial pool of collagen maintains tissue function.


Assuntos
Relógios Circadianos/fisiologia , Colágeno/metabolismo , Homeostase/fisiologia , Via Secretória/fisiologia , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/efeitos dos fármacos , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Carbazóis/farmacologia , Colágeno/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Matriz Extracelular/metabolismo , Camundongos Transgênicos , Pirrolidinas/farmacologia , Canais de Translocação SEC/efeitos dos fármacos , Canais de Translocação SEC/metabolismo , Via Secretória/genética , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Proteínas de Transporte Vesicular/efeitos dos fármacos , Proteínas de Transporte Vesicular/metabolismo
9.
Int J Biol Macromol ; 142: 680-692, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622708

RESUMO

Bacterial biofilms on wounds impair the healing process and often lead to chronic wounds. Chitosan is a well-known biopolymer with antimicrobial and anti-biofilm effects. S-nitrosoglutathione (GSNO) has been identified as a promising nitric oxide (NO) donor to defend against pathogenic biofilms and enhance wound healing activities. In this study, we prepared NO-releasing chitosan film (CS/NO film) and evaluated its anti-biofilm activity and in vivo wound healing efficacy against methicillin-resistant Staphylococcus aureus (MRSA) biofilm-infected wounds in diabetic mice. The in vitro release study showed sustained release of NO over 3 days in simulated wound fluid. The CS/NO film significantly enhanced antibacterial activity against MRSA by > 3 logs reduction in bacterial viability. Moreover, CS/NO film exhibited a 3-fold higher anti-biofilm activity than the control and CS film. In in vivo MRSA biofilm-infected wounds, the CS/NO film-treated group showed faster biofilm dispersal, wound size reduction, epithelialization rates, and collagen deposition than the untreated and CS film-treated groups. Therefore, the CS/NO film investigated in this study could be a promising approach for the treatment of MRSA biofilm-infected wounds.


Assuntos
Antibacterianos/química , Quitosana/química , Óxido Nítrico/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Bandagens , Biofilmes , Linhagem Celular , Sobrevivência Celular , Colágeno/efeitos dos fármacos , Diabetes Mellitus Experimental , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hidrogéis/química , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/farmacologia
10.
Ann Surg ; 272(1): 183-193, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-30585822

RESUMO

OBJECTIVE: To investigate the effects of local doxycycline administration on skin scarring. BACKGROUND: Skin scarring represents a major source of morbidity for surgical patients. Doxycycline, a tetracycline antibiotic with off-target effects on the extracellular matrix, has demonstrated antifibrotic effects in multiple organs. However, doxycycline's potential effects on skin scarring have not been explored in vivo. METHODS: Female C57BL/6J mice underwent dorsal wounding following an established splinted excisional skin wounding model. Doxycycline was administered by local injection into the wound base following injury. Wounds were harvested upon complete wound closure (postoperative day 15) for histological examination and biomechanical testing of scar tissue. RESULTS: A one-time dose of 3.90 mM doxycycline (2 mg/mL) within 12 hours of injury was found to significantly reduce scar thickness by 24.8% (P < 0.0001) without compromising tensile strength. The same effect could not be achieved by oral dosing. In doxycycline-treated scar matrices, collagen I content was significantly reduced (P = 0.0317) and fibers were favorably arranged with significantly increased fiber randomness (P = 0.0115). Common culprits of altered wound healing mechanics, including angiogenesis and inflammation, were not impacted by doxycycline treatment. However, engrailed1 profibrotic fibroblasts, responsible for scar extracellular matrix deposition, were significantly reduced with doxycycline treatment (P = 0.0005). CONCLUSIONS: Due to the substantial improvement in skin scarring and well-established clinical safety profile, locally administered doxycycline represents a promising vulnerary agent. As such, we favor rapid translation to human patients as an antiscarring therapy.


Assuntos
Cicatriz/prevenção & controle , Colágeno/efeitos dos fármacos , Doxiciclina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Doxiciclina/administração & dosagem , Feminino , Injeções Intralesionais , Camundongos , Camundongos Endogâmicos C57BL , Resistência à Tração
11.
Braz J Med Biol Res ; 53(1): e8621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31859909

RESUMO

The use of specially designed wound dressings could be an important alternative to facilitate the healing process of wounds in the hyperglycemic state. Biocompatible dressings combining chitosan and alginate can speed up wound healing by modulating the inflammatory phase, stimulating fibroblast proliferation, and aiding in remodeling phases. However, this biomaterial has not yet been explored in chronic and acute lesions of diabetic patients. The aim of this study was to evaluate the effect of topical treatment with a chitosan-alginate membrane on acute skin wounds of hyperglycemic mice. Diabetes mellitus was induced by streptozotocin (60 mg · kg-1 · day-1 for 5 days, intraperitoneally) and the cutaneous wound was performed by removing the epidermis using a surgical punch. The results showed that after 10 days of treatment the chitosan and alginate membrane (CAM) group exhibited better organization of collagen fibers. High concentrations of interleukin (IL)-1α, IL-1ß, granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α) were detected in the first and second days of treatment. G-CSF and TNF-α level decreased after 5 days, as well as the concentrations of TNF-α and IL-10 compared with the control group (CG). In this study, the inflammatory phase of cutaneous lesions of hyperglycemic mice was modulated by the use of CAM, mostly regarding the cytokines IL-1α, IL-1ß, TNF-α, G-CSF, and IL-10, resulting in better collagen III deposition. However, further studies are needed to better understand the healing stages associated with CAM use.


Assuntos
Alginatos/administração & dosagem , Bandagens , Proliferação de Células/efeitos dos fármacos , Quitosana/administração & dosagem , Diabetes Mellitus Experimental/fisiopatologia , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/administração & dosagem , Biomarcadores/sangue , Colágeno/efeitos dos fármacos , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo
12.
Acta Cir Bras ; 34(9): e201900901, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800678

RESUMO

PURPOSE: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. METHODS: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. RESULTS: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). CONCLUSIONS: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.


Assuntos
Pênis/irrigação sanguínea , Pênis/inervação , Traumatismos dos Nervos Periféricos/prevenção & controle , Inibidores da Fosfodiesterase 5/farmacologia , Substâncias Protetoras/farmacologia , Tadalafila/farmacologia , Animais , Colágeno/análise , Colágeno/efeitos dos fármacos , Tecido Elástico/anatomia & histologia , Tecido Elástico/efeitos dos fármacos , Disfunção Erétil/prevenção & controle , Imuno-Histoquímica , Masculino , Pênis/efeitos dos fármacos , Pênis/patologia , Prostatectomia/efeitos adversos , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes
13.
Arq Bras Cir Dig ; 32(3): e1457, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31826084

RESUMO

BACKGROUND: Manipulating intestinal microbiota with probiotics might stimulate skin response. Understanding all stages of the healing process, as well as the gut-skin-healing response can improve the skin healing process. AIM: To evaluate the effect of perioperative oral administration of probiotics on the healing of skin wounds in rats. METHODS: Seventy-two Wistar male adult rats were weighed and divided into two groups with 36 each, one control group (supplemented with oral maltodextrin 250 mg/day) and one probiotic group (supplemented with Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM® at a dose of 250 mg/day), both given orally daily for 15 days. The two groups were subsequently divided into three subgroups according to the moment of euthanasia: in the 3rd, 7th and 10th postoperative days. RESULTS: There were no significant changes in weight in both groups. Wound contraction was faster in probiotic group when compared to the controls, resulting in smaller wound area in the 7th postoperative day. As for histological aspects, the overall H&E score was lower in the probiotic group. The probiotic group showed increased fibrosis from 3rd to the 7th postoperative day. The type I collagen production was higher in the probiotic group at the 10th postoperative day, and the type III collagen increased in the 7th. CONCLUSION: The perioperative use of orally administrated probiotic was associated with a faster reduction of the wound area in rats probably by reducing the inflammatory phase, accelerating the fibrosis process and the deposition of collagen.


Assuntos
Colágeno/efeitos dos fármacos , Suplementos Nutricionais , Probióticos/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Oral , Animais , Masculino , Ratos , Ratos Wistar
14.
Int. j. morphol ; 37(4): 1416-1421, Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040147

RESUMO

The indiscriminate use of anabolic steroids in gyms has been growing in a generalized way, among which, the most common is growth hormone (GH). In the short term GH may potentiate muscle growth, especially when taken in combination with resistance training. However, the effects of this hormone are not yet fully understood in the literature, especially in relation to collagen properties. The objective of this study was to evaluate the effect of the application of growth hormone (GH) and resistance training (RT) on the collagen properties of femoral bone tissue using Raman Spectroscopy. In this study 40 male rats were randomly distributed into four groups (n=10): control (C), control and GH application (GH), resistance training (T), and resistance training and GH application (GHT). The training consisted of four series of 10 water jumps, performed three times a week, with an overload corresponding to 50 % of body weight and duration of four weeks. GH was applied at a dosage of 0.2 IU/Kg (0.067 mg/kg) to each animal, three times a week, every other day. The animals were euthanized and the right femurs were collected for analysis of bone structure. Raman spectroscopy (RS) was used to observe the following compounds from their respective bands: type I collagen (662 cm-1), amide III (1243 cm-1), proteins including type I collagen (1278 cm-1), woven collagen (1322 cm-1), association of collagen, phospholipids, nucleic acid, and phosphate (1330 cm-1), and collagen and protein deformation (1448 cm-1). The results demonstrated an increase in the collagen properties in all analyzed variables, however, the T group presented a statistically significant difference (p<0.05). It is possible to conclude that isolated physical training was shown to be more efficient than when combined with the application of GH to increase the collagen properties of the femoral bone tissue.


El uso indiscriminado de anabolizantes en los gimnasios ha aumentado de forma generalizada, entre éstos la hormona de crecimiento (HC) es una de las más utilizadas, y a corto plazo puede potencializar el crecimiento muscular, principalmente cuando es realizado en combinación con el entrenamiento de fuerza. Sin embargo, los efectos de esta hormona aún no están totalmente esclarecidos en la literatura, especialmente en relación a las propiedades colágenas. El objetivo del estudio fue evaluar el efecto de la aplicación del HC y entrenamiento de fuerza (E) en las propiedades colágenas del tejido óseo femoral a partir de la utilización de la espectroscopía Raman. Se usaron 40 ratas Wistar distribuidos en cuatro grupos (n=10): control (C), control y aplicación del HC (HCC), entrenamiento de fuerza (E) y entrenamiento de fuerza y aplicación del HC (THC). El entrenamiento fue compuesto por cuatro series de 10 saltos acuáticos, realizados tres veces por semana, con sobrecarga correspondiente a 50 % del peso corporal y duración de cuatro semanas. El HC fue aplicado en una dosificación de 0,2 UI/Kg (0,067 mg/kg) en cada animal, tres veces por semana, en días no consecutivos. Los animales fueran eutanasiados y se retiró el fémur derecho para realización del análisis de la estructura ósea. La espectroscopía Raman (ER) fue utilizada para observar los siguientes compuestos a partir de las respectivas bandas: colágeno tipo I (662 cm-1), amida III (1243 cm1), proteínas, incluido colágeno tipo I (1278 cm-1), colágeno retorcido (1322 cm-1), asociación de colágeno, fosfolípidos, ácidos nucleicos y fosfato (1330 cm-1), deformación de colágeno y proteína (1448 cm-1). Hubo aumento en las propiedades colágenas en todas las variables analizadas, sin embargo, solamente el grupo E demostró una diferencia estadísticamente significativa (p<0,05). En conclusión, para el aumento de las propiedades colágenas del tejido óseo femoral, el entrenamiento físico aislado es más eficiente que el entrenamiento combinado con el uso de HC.


Assuntos
Animais , Masculino , Ratos , Resistência Física/fisiologia , Hormônio do Crescimento/farmacologia , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Hormônio do Crescimento/administração & dosagem , Exercício Físico/fisiologia , Colágeno/efeitos dos fármacos , Ratos Wistar , Microscopia/métodos
15.
Int Wound J ; 16(6): 1281-1288, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31475447

RESUMO

Immunological factors play important roles in the occurrence of hypertrophic scars. Imiquimod can be used as an immunosuppressive agent to regulate the function of T-helper (Th) cell subsets Th1 and Th2. In this article, we explored the impact of imiquimod on scar hyperplasia through Th cells. A rabbit ear hypertrophic scar model was built. Four round wounds were cut in each rabbit's ears ventrally with a diameter of 1 cm and bilateral symmetry. All the right ear wounds were treated with 5% imiquimod cream. The blank control group contained all the left ear wounds, which were treated with Vaseline ointment at the same time. Haematoxylin and eosin and Masson staining showed that imiquimod collagen deposition was significantly reduced compared with the control group, scar index (SEI) showed that the proliferative degree reached its peak on the 28th day after operation in blank group, and the degree of hyperplasia was significantly higher than that of the imiquimod group (P < .05). Real-time Polymerase chain reaction results showed that the imiquimod induced the expression of Th2 cell-related chemokines CCL2, CCL3, CCL5, CCL7, and CCL13 at each time point, which were significantly lower than that of the blank control group, and the expressions of Th1 cell-associated chemokines CXCL10 and CXCL12 at each time point was significantly higher than the blank control group (P < .05). Imiquimod can be used to regulate the expression of Th1 and Th2 cell-associated chemokines to control scar hyperplasia.


Assuntos
Adjuvantes Imunológicos/farmacologia , Quimiocinas/metabolismo , Cicatriz Hipertrófica/tratamento farmacológico , Imiquimode/farmacologia , Animais , Quimiocinas/genética , Cicatriz Hipertrófica/metabolismo , Colágeno/efeitos dos fármacos , Colágeno/ultraestrutura , Modelos Animais , Pomadas , RNA Mensageiro/metabolismo , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Células Th1/metabolismo , Células Th2/metabolismo
16.
Braz J Med Biol Res ; 52(9): e8290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482998

RESUMO

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Colágeno/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Animais , Colágeno/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Tenotomia , Cicatrização/efeitos dos fármacos
17.
Neurourol Urodyn ; 38(8): 2159-2169, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31541501

RESUMO

AIM: We investigated the effects of Ba-Wei-Die-Huang-Wan (BWDHW) on ketamine-induced cystitis (KIC) in a rat model. METHODS: Female Sprague-Dawley rats were distributed into three groups: control (saline), ketamine (25 mg/kg/day for 28 days), or ketamine (25 mg/kg/day for 28 days) plus BWDHW (90 mg/kg/day, started from day 14). Functional magnetic resonance imaging (fMRI), metabolic cage study, and cystometry were evaluated. Bladder histology was evaluated. Western blots of the bladder proteins were carried out. RESULTS: Compared with controls, ketamine-treated rats showed stronger fMRI intensity in the periaqueductal gray area and bladder overactivity in the bladder functional study, but the ketamine/BWDHW-treated rats did not. Furthermore, ketamine breached the uroplakin III membrane at the apical surface of the urothelium, enhanced substance P spread over the urothelium, induced suburothelial hemorrhage and monocyte/macrophage infiltration, and caused interstitial fibrosis deposition. By contrast, the BWDHW-treated rats exhibited less substance P spread, lower suburothelial monocyte/macrophage infiltration, and lower interstitial fibrosis deposition. The ketamine group showed significant overexpression of neuroreceptors in the bladder mucosa (the transient receptor potential vanilloid 1 and M2 - and M3 -muscarinic receptors) and detrusor (M2 - and M3 -muscarinic receptors); inflammatory mediators in the detrusor (interleukin-1ß [IL-1ß], IL-6, tumor necrosis factor-α, nuclear factor-κB, cyclooxygenase-2, and intercellular adhesion molecule-1); and fibrogenesis molecules in the detrusor (transforming growth factor-ß1, collagen I, collagen III, and fibronectin). However, no significant changes were noted between the ketamine/BWDHW and control groups. CONCLUSION: BWDHW could exert therapeutic effects by inhibiting the upregulation of neuroreceptors, modulating inflammatory mediators, suppressing fibrogenesis, and ameliorating bladder overactivity in rats with KIC.


Assuntos
Cistite/induzido quimicamente , Medicamentos de Ervas Chinesas/farmacologia , Ketamina/efeitos adversos , Bexiga Urinária Hiperativa/induzido quimicamente , Bexiga Urinária/efeitos dos fármacos , Urotélio/efeitos dos fármacos , Animais , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Cistite/metabolismo , Cistite/patologia , Cistite/fisiopatologia , Feminino , Fibronectinas/efeitos dos fármacos , Fibronectinas/metabolismo , Neuroimagem Funcional , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Imagem por Ressonância Magnética , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Substância Cinzenta Periaquedutal/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/metabolismo , Células Receptoras Sensoriais , Substância P/efeitos dos fármacos , Substância P/metabolismo , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/metabolismo , Bexiga Urinária Hiperativa/patologia , Bexiga Urinária Hiperativa/fisiopatologia , Urotélio/metabolismo
18.
Arthritis Rheumatol ; 71(11): 1923-1934, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31173491

RESUMO

OBJECTIVE: To assess the preclinical efficacy and mechanism of action of an anti-CX3 CL1 monoclonal antibody (mAb) in systemic sclerosis (SSc). METHODS: Cultured human dermal fibroblasts were used to evaluate the direct effect of anti-CX3 CL1 mAb on fibroblasts. In addition, bleomycin-induced and growth factor-induced models of SSc were used to investigate the effect of anti-CX3 CL1 mAb on leukocyte infiltration, collagen deposition, and vascular damage in the skin. RESULTS: Anti-CX3 CL1 mAb treatment significantly inhibited Smad3 phosphorylation (P < 0.05) and expression of type I collagen and fibronectin 1 (P < 0.01) in dermal fibroblasts stimulated with transforming growth factor ß1 (TGFß1). In the bleomycin model, daily subcutaneous bleomycin injection increased serum CX3 CL1 levels (P < 0.05) and augmented lesional CX3 CL1 expression. Simultaneous administration of anti-CX3 CL1 mAb or CX3 CR1 deficiency significantly suppressed the dermal thickness, collagen content, and capillary loss caused by bleomycin (P < 0.05). Injection of bleomycin induced expression of pSmad3 and TGFß1 in the skin, which was inhibited by anti-CX3 CL1 mAb. Further, the dermal infiltration of CX3 CR1+ cells, macrophages (inflammatory and alternatively activated [M2-like] subsets), and CD3+ cells significantly decreased following anti-CX3 CL1 mAb therapy (P < 0.05), as did the enhanced skin expression of fibrogenic molecules, such as thymic stromal lymphopoietin and secreted phosphoprotein 1 (P < 0.05). However, the treatment did not significantly reduce established skin fibrosis. In the second model, simultaneous anti-mCX3 CL1 mAb therapy significantly diminished the skin fibrosis induced by serial subcutaneous injection of TGFß and connective tissue growth factor (P < 0.01). CONCLUSION: Anti-CX3 CL1 mAb therapy may be a novel approach for treating early skin fibrosis in inflammation-driven fibrotic skin disorders such as SSc.


Assuntos
Anticorpos Monoclonais/farmacologia , Receptor 1 de Quimiocina CX3C/imunologia , Capilares/efeitos dos fármacos , Quimiocina CX3CL1/antagonistas & inibidores , Colágeno/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Escleroderma Sistêmico/imunologia , Pele/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Capilares/patologia , Quimiocina CX3CL1/imunologia , Colágeno/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Fibroblastos/patologia , Fibrose/induzido quimicamente , Humanos , Técnicas In Vitro , Inflamação , Camundongos , Escleroderma Sistêmico/patologia , Transdução de Sinais , Pele/imunologia , Pele/patologia , Proteína Smad3/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta3/toxicidade
19.
Can J Cardiol ; 35(4): 480-489, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935639

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as important mediators of cardiac pathophysiology. The aim of the present study is to investigate the effects of lncR-30245, an lncRNA, on cardiac fibrogenesis and the underlying mechanism. METHODS: Myocardial infarction (MI) and transforming growth factor (TGF)-ß1 were used to induce fibrotic phenotypes. Cardiac fibrosis was detected by Masson's trichrome staining. Cardiac function was evaluated by echocardiography. Western blot, quantitative reverse transcription-polymerase chain reaction, and pharmacological approaches were used to investigate the role of lncR-30245 in cardiac fibrogenesis. RESULTS: Expression of lncR-30245 was significantly increased in MI hearts and TGF-ß1-treated cardiac fibroblasts (CFs). LncR-30245 was mainly located in the cytoplasm. Overexpression of lncR-30245 promoted collagen production and CF proliferation. Knockdown of lncR-30245 significantly inhibited TGF-ß1-induced collagen production and CF proliferation. LncR-30245 overexpression inhibited the antifibrotic role of peroxisome proliferator-activated receptor (PPAR)-γ and increased connective tissue growth factor (CTGF) expression, whereas lncR-30245 knockdown exerted the opposite effects. Rosiglitazone, a PPAR-γ agonist, significantly inhibited lncR-30245-induced CTGF upregulation and collagen production in CFs. In contrast, T0070907, a PPAR-γ antagonist, attenuated the inhibitory effects of lncR-30245 small interfering RNA (siRNA) on TGF-ß1-induced CTGF expression and collagen production. LncR-30245 knockdown significantly enhanced ejection fraction and fractional shortening and attenuated cardiac fibrosis in MI mice. CONCLUSION: Our study indicates that the lncR-30245/PPAR-γ/CTGF pathway mediates MI-induced cardiac fibrosis and might be a therapeutic target for various cardiac diseases associated with fibrosis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Cardiopatias/metabolismo , PPAR gama/metabolismo , RNA Longo não Codificante , Animais , Benzamidas/farmacologia , Proliferação de Células , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Fibroblastos/metabolismo , Fibrose , Camundongos Endogâmicos C57BL , Modelos Animais , Infarto do Miocárdio/metabolismo , Piridinas/farmacologia , Rosiglitazona/farmacologia , Volume Sistólico , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima/efeitos dos fármacos
20.
Burns ; 45(5): 1139-1151, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30833099

RESUMO

Third-degree or full-thickness burns refer to lesions that extend to the epidermis, dermis, and subcutaneous tissue. The pathophysiology of burn wounds is characterized by tissue inflammation, edema, and hypertrophic scarring. Farnesol is a natural 15-carbon organic compound that possesses many biological effects. We have previously demonstrated that farnesol gel exerts restorative actions on ultraviolet B (UVB)-caused sunburn in vivo. The in vitro results revealed that liposomal farnesol from 0.04mM to 0.8mM significantly enhanced collagen production by murine skin fibroblasts, whereas liposomal farnesol at high (0.8mM) and low concentration (0.04mM) did not show any suppressions on skin fibroblast proliferation. We treated third-degree burns on a rat model with a formulated gel composed of various ratios of 2% hydroxypropyl methylcellulose (HPMC) and 4mM liposomal farnesol for 7 and 14 days. On days 7 and 14 post wounding, histopathological observations revealed that the HPMC:farnesol gel ratios of 1:2 and 2:1 exerted the greatest tissue-repairing effects on the skin after third-degree burns compared with skin untreated or treated with a commercial burn gel and HPMC alone. These findings were consistent with the in vivo quantitative collagen-producing assay, wound healing scoring, and IL-6 Western blot results. These findings demonstrated that the fabricated liposomal farnesol gel is potentially able to promote wound healing after third-degree burns.


Assuntos
Queimaduras/patologia , Colágeno/efeitos dos fármacos , Farneseno Álcool/farmacologia , Pele/patologia , Cicatrização/efeitos dos fármacos , Animais , Queimaduras/metabolismo , Colágeno/metabolismo , Farneseno Álcool/administração & dosagem , Derivados da Hipromelose , Interleucina-6/metabolismo , Lipossomos/ultraestrutura , Microscopia Eletrônica de Transmissão , Ratos
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