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1.
J Photochem Photobiol B ; 203: 111744, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31887637

RESUMO

Articular cartilage regeneration is a challenging process due to its inadequate ability of self-recovering biological mechanisms. The progresses of cartilage tissue engineering is supported to overwhelmed the repairing difficulties and degenerative diseases. The main goal of the present study is to design biomaterials with suitable physico-chemical, mechanical and biological properties for the carrier of growth factor and improving differentiation of mesenchymal stem cell into damaged cartilage tissues. Herein, TGF-ß loaded hydrogel network was prepared through the chemical interactions between vinyl group of natural polymers. Fourier-transform infrared spectroscopy results show the characteristic peaks at 3074 cm-1, 1713 cm-1, and 810 cm-1, which confirm the existence of the vinyl group and successful formation of maleoyl functionalized Chitosan (MCh). The obtained MCh was freely dissolved in the distilled water up to 8% (w/v). X-ray photoelectron spectroscopy survey spectral results show a peak at 289.0 eV which revealed that the OCO and DS were 1.2% and also evidenced the methacryl substitution of Silk fibroin (SF) nanoformulations. The weight loss and mechanical test were analyzed and the results showed that MSF acts as a foremost crosslinking point with MCh through the reaction between the methacrylate groups of MSF and maleoyl groups of MCh which led to enhancing the density and improved the compressive strength. The maximum drug release activity was recorded in the TGF-ß loaded MCh@MSF hydrogel compared to bare MCh hydrogel. Further, the TGF-ß loaded MCh@ MSF hydrogel exhibited the cell viability percentage nearly at 79-102% for MC3T3-E1 and 88-104% for BMDSCs. Similarly, the TGF-ß loaded MCh@MSF exhibited the highest inhibitory activity against E. coli (83%) than S. aureus (67%). Overall, this study concluded the TGF-ß loaded MCh@MSF showed better biocompatibility and could be utilized in the field of cartilage tissue engineering.


Assuntos
Cartilagem Articular/fisiologia , Quitosana/química , Hidrogéis/química , Regeneração , Seda/química , Fator de Crescimento Transformador beta/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Nanopartículas/química , Regeneração/efeitos dos fármacos , Reologia , Staphylococcus aureus/efeitos dos fármacos , Engenharia Tecidual , Fator de Crescimento Transformador beta/química
2.
Georgian Med News ; (292-293): 87-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560670

RESUMO

Hematological disorders caused by radiation remain the most challenging problem of the last decades. Environmental radiation, as well as medical application of radiation causes serious problems especially from the point of view of blood formation and passage of blood functional cells. Bone marrow emptying followed by the rise of immature cells in the bloodstream is the main pathology that must be eliminated. The importance of the issue is well recognized by all investigators. Opening of agents for regulation of spontaneous regeneration of hematopoietic cell lines is of prime importance in cancer treatment. Ubiquitin is a globular protein of eukaryotic cells. It is involved in regulation of cell cycle. Recently we studied the influence of extracellular ubiquitin on regeneration of leukopoiesis. Interestingly what is its effect on erythropoietic cell lines? Erythrocytes are more resistant to irradiation, than nucleic cells. Their depletion-elevation picks during blood regeneration clearly reveal low sharpness. Nevertheless, depletion of erythropoietic cells if not treated, may cause short- and long-term side effects. We studied the influence of intraperitoneally injected ubiquitin on the process of spontaneous regeneration of erythropoietic cell lines of bone marrow (BM) and peripheral blood (PB) after irradiation in mice. The source of radiation was 137Cs with dose rate 1Gy/min., the duration of exposure 3 min and 5 min. Nonlinear white mice of 22±2 gr. were used for experiment. Animals were divided into five groups (6 animals in each group): the first control group of intact mice; the second test group of mice irradiated by the sublethal dose of 3Gy; the third test group of mice irradiated by 3Gy intraperitoneally injected by ubiquitin by the dose of 100µg/ml at the 72 hour point after irradiation; the fourth test group of mice irradiated by the dose of LD50 5Gy; the fifth test group of mice irradiated by 5Gy intraperitoneally injected by ubiquitin at the 72 hour point after irradiation. PB and BM samples from the control group and the test groups of mice have been taken every 24 hours after irradiation during 7 days. Microscopy and statistical methods have been implicated for calculation of cell count of PB and BM. Analyzing the results we concluded that Ubiquitin prevents depletion-elevation picks of erythrocytes and erythroblasts regardless of the severity of damage caused by different doses of radiation indicating normalization of the regeneration process after irradiation. The study is important for opening new therapeutic agents for normalization of regeneration hematopoiesis after irradiation.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Radioisótopos de Césio , Hematopoese/efeitos dos fármacos , Lesões Experimentais por Radiação , Regeneração/efeitos dos fármacos , Ubiquitina/farmacologia , Animais , Ciclo Celular/efeitos da radiação , Camundongos , Ubiquitina/administração & dosagem
3.
Ecotoxicol Environ Saf ; 185: 109680, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31546204

RESUMO

The freshwater planarian mostly lives in the upper reaches of springs and rivers. Generally, it is realized as a suitable warning indicator of environmental toxicants. The freshwater planarian Dugesia japonica has a powerful regenerative capability and can regenerate a new individual including a complete central nervous system in one week. Rapamycin is an inhibitor of mammalian TORC1 (target of rapamycin complex-1) and used in the treatment of some diseases like cancer, cardiovascular and neurological diseases. However, the roles of rapamycin in the regulation of planarian regeneration remain to be elucidated. In present study, freshwater planarians D. japonica were firstly treated with 1 µM rapamycin for 18 h exposures and the expression patterns of Djtor was analyzed by the whole-mount in situ hybridization (WISH). Our results indicated rapamycin could strongly inhibit Djtor expression in planarian D. japonica and cause asymmetric blastemas and neuronal defects in planarians. Furthermore, knockdown of Djtor gene in planarians using RNA interference resulted in the suppression of downstream autophagy genes. These findings suggested that rapamycin might regulate freshwater planarian regeneration via Djtor signaling pathway.


Assuntos
Planárias/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Sirolimo/toxicidade , Serina-Treonina Quinases TOR/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Sistema Nervoso Central/efeitos dos fármacos , Neurônios , Planárias/genética , Planárias/crescimento & desenvolvimento , Planárias/metabolismo , Interferência de RNA , Regeneração/fisiologia , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
4.
Mater Sci Eng C Mater Biol Appl ; 104: 109924, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499991

RESUMO

We report the first experimental evidence for the mitogenic action of cerium(IV) oxide and cerium(III) fluoride nanoparticles (CONs and CFNs) on the regeneration of a whole organism - freshwater flatworms Schmidtea mediterranea (planarian). Both types of cerium-containing nanoparticles are shown to be a highly potent mitogen for planaria. Both CONs and CFNs, in micro- and nanomolar concentrations, markedly accelerate planarian blastema growth, due to the enhancement of cellular proliferation, causing an increase in the mitotic index and in the quantity of blastema cells in regenerating planaria. CONs provided maximum activity at concentrations which were two orders of magnitude lower than those for CeF3. The valence state of cerium in cerium-containing nanoparticles plays a significant role in the planarian regeneration mechanism: CeO2 nanoparticles containing predominantly Ce4+ species presumably scavenge wound induced reactive oxygen species and moderately activate gene expression processes, while the regenerative action of CeF3 nanoparticles containing only Ce3+ species is manifested in the pronounced expression of the genes involved in cell division, differentiation and migration. This is the first report on the effect of cerium-containing nanoparticles on tissue regeneration in vivo, further revealing the mechanisms of their biological action, which enhances the possibility of their use in cellular technologies.


Assuntos
Cério/farmacologia , Fluoretos/farmacologia , Compostos Inorgânicos/farmacologia , Mitógenos/farmacologia , Nanopartículas/química , Planárias/citologia , Planárias/fisiologia , Regeneração/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , DNA/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Instabilidade Genômica , Cabeça , Mitose/efeitos dos fármacos , Mutagênicos/toxicidade , Planárias/efeitos dos fármacos , Planárias/genética , Testes de Toxicidade
5.
Adv Exp Med Biol ; 1178: 155-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493227

RESUMO

Skin aging is a complex process induced by intrinsic and extrinsic factors and causes alterations to the structural and functional aspects of the skin. Skin aging affects patients physically and physiologically. Understanding the process of skin aging can provide new knowledge on how to attenuate or reduce skin disorder symptoms. Herbs have been used for ages to prevent and treat skin aging, yet there are growing interests by researchers in this field globally. Various strategies have been developed for improving the quality and effectivity of herbal skin care products, both for topical and oral applications. This review will provide an overview of the relationship between herbal skin care products and the skin aging process.


Assuntos
Preparações de Plantas , Regeneração , Envelhecimento da Pele , Fenômenos Fisiológicos da Pele , Humanos , Preparações de Plantas/farmacologia , Regeneração/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Higiene da Pele , Fenômenos Fisiológicos da Pele/efeitos dos fármacos
6.
Biol Pharm Bull ; 42(9): 1446-1449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474706

RESUMO

During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.


Assuntos
Flavonoides/farmacologia , Cor de Cabelo , Folículo Piloso/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Animais , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/fisiologia , Flavonoides/química , Folículo Piloso/fisiologia , Luteolina/química , Luteolina/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/fisiologia , Camundongos Endogâmicos C57BL , Pele/efeitos dos fármacos , Relação Estrutura-Atividade
7.
Artif Cells Nanomed Biotechnol ; 47(1): 3423-3430, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31402711

RESUMO

A novel nerve conductor made out of polypyrrole (PPY), collagen (Coll) and nano-strontium substituted bioactive glass (n-Sr@BG) (PPY/Coll/n-Sr@BG) was fabricated by electrospinning. SEM demonstrated that the mean distances across of the pores in the nerve channels were under 15 mm and more prominent than 2 mm. These biocomposite films had biomimetic morphology, bigger porosity and moderately higher surface territory than customary nerve channels, consequently not just allowing the transportation of nerve development factor and glucose yet, in addition, hindering the section of lymphatic tissue and fibroblasts. The consistent filaments of the nerve can copy the characteristic ECM, which is valuable to cell bond, cell multiplication, and cell movement. PPY/Coll/n-Sr@BG demonstrated great cell fondness rate, which is useful for neurilemma cell cells bond, relocation and expansion. Its great viability empowers its wellbeing animal models. Sciatic nerve deformity was crossed over an animal model with PPY/Coll/n-Sr@BG in rodents. PPY/Coll and autotransplants were utilized as control gatherings. Contrasted with PPY/Coll and PPY/Coll/n-Sr@BG accomplished fundamentally increasingly viable recovery of sciatic nerve wounds following 24 weeks implantation and the mean distance across of muscle fibres occasions bigger than that in PPY/Coll/n-Sr@BG, and it was nearer to that in control. The rejuvenated nerve filaments in PPY/Coll/n-Sr@BG had an increasingly standard round shape, the thickness of neuro-filaments in c was more than those in PPY/Coll, and was near that in control.


Assuntos
Materiais Biocompatíveis/farmacologia , Colágeno/química , Vidro/química , Polímeros/química , Pirróis/química , Regeneração/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Estrôncio/química , Animais , Materiais Biocompatíveis/química , Eletricidade , Humanos , Nanoestruturas/química , Nanotecnologia , Nervo Isquiático/fisiologia
8.
Nat Commun ; 10(1): 3667, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413255

RESUMO

Receptor type protein tyrosine phosphatase-sigma (PTPσ) is primarily expressed by adult neurons and regulates neural regeneration. We recently discovered that PTPσ is also expressed by hematopoietic stem cells (HSCs). Here, we describe small molecule inhibitors of PTPσ that promote HSC regeneration in vivo. Systemic administration of the PTPσ inhibitor, DJ001, or its analog, to irradiated mice promotes HSC regeneration, accelerates hematologic recovery, and improves survival. Similarly, DJ001 administration accelerates hematologic recovery in mice treated with 5-fluorouracil chemotherapy. DJ001 displays high specificity for PTPσ and antagonizes PTPσ via unique non-competitive, allosteric binding. Mechanistically, DJ001 suppresses radiation-induced HSC apoptosis via activation of the RhoGTPase, RAC1, and induction of BCL-XL. Furthermore, treatment of irradiated human HSCs with DJ001 promotes the regeneration of human HSCs capable of multilineage in vivo repopulation. These studies demonstrate the therapeutic potential of selective, small-molecule PTPσ inhibitors for human hematopoietic regeneration.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/antagonistas & inibidores , Regeneração/efeitos dos fármacos , Regulação Alostérica , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos da radiação , Fluoruracila/farmacologia , Células-Tronco Hematopoéticas/efeitos da radiação , Humanos , Camundongos , Radiação , Regeneração/efeitos da radiação , Proteína bcl-X/efeitos dos fármacos , Proteína bcl-X/metabolismo , Proteínas rac1 de Ligação ao GTP/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/metabolismo
9.
Tissue Cell ; 59: 1-9, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383283

RESUMO

The effect of the GM6001 metalloproteinase inhibitor on the regeneration of ambulacral structures in Eupentacta fraudatrix has been investigated. Inhibition of proteinase activity exerts a marked effect on regeneration, being dependent on the time when GM6001 is injected. When administration of the inhibitor begins on day 3 post-injury, regeneration is completely abolished, and the animals die. This means that early activation of proteinases is crucial for triggering the regenerative process in holothurians. When GM6001 in first injected on day 7 post-injury, the regeneration rate decreases. However, this effect has proven to be reversible: when inhibition ceases, the regeneration resumes. The effect of the inhibitor is manifested as a retarded degradation of the extracellular matrix, the lack of cell dedifferentiation, and, probably, a slower cell migration. The gelatinase activity is detected in all the regenerating organs of E. fraudatrix. In the holothurian Cucumaria japonica, which is not capable of healing skin wounds and ambulacrum reparation, no gelatinase activity was observed at the site of damage. A suggestion is made that proteinases play an important role in regeneration in holothurians. The most probable morphogenesis regulators are matrix metalloproteinases with gelatinase activity.


Assuntos
Dipeptídeos/farmacologia , Gelatinases/antagonistas & inibidores , Holothuria/fisiologia , Inibidores de Metaloproteinases de Matriz/farmacologia , Regeneração/efeitos dos fármacos , Animais , Gelatinases/metabolismo , Regeneração/fisiologia
10.
Cell Prolif ; 52(5): e12666, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31407423

RESUMO

OBJECTIVES: Cartilaginous tissue degradation occurs because of the lack of survival of chondrocytes. Here, we ascertained whether bakuchiol (BAK) has the capability of activating chondrocyte proliferation. MATERIALS AND METHODS: The effect of BAK on the proliferation of rat chondrocytes at a concentration of 10 and 20 µmol/L was investigated. The molecular mechanisms involving target binding and signalling pathways were elucidated by RNA-sequencing, qPCR, molecular docking and Western blotting. Matrigel mixed with bakuchiol was implanted locally into rat knee articular cartilage defects to verify the activation of chondrocytes due to bakuchiol in vivo. RESULTS: Bakuchiol implantation resulted in the activation of rat chondrocyte proliferation in a dose-dependent manner. RNA-sequencing revealed 107 differentially expressed genes (DEGs) with 75 that were up-regulated and 32 that were down-regulated, indicating increased activation of the PI3K-Akt and cell cycle pathways. Activation of the phosphorylation of Akt, ERK1/2 and their inhibitors blocked the proliferative effect of bakuchiol treatment, confirming its direct involvement in these signal transduction pathways. Molecular docking and siRNA silencing revealed that estrogen receptor-α (ERα) was the target of bakuchiol in terms of its cell proliferative effect via PI3K activation. Two weeks after implantation of bakuchiol, the appearance and physiological structure of the articular cartilage was more integrated with abundant chondrocytes and cartilage matrix compared to that of the control. CONCLUSIONS: Bakuchiol demonstrated significant bioactivity towards chondrocyte proliferation via the PI3K-Akt and ERK1/2 pathways mediated by estrogen receptor activation and exhibited enhanced promotion of the remodelling of injured cartilage.


Assuntos
Cartilagem Articular/fisiologia , Proliferação de Células/efeitos dos fármacos , Fenóis/farmacologia , Receptores Estrogênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Condrócitos/citologia , Condrócitos/metabolismo , Regulação para Baixo/efeitos dos fármacos , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos
11.
Nat Commun ; 10(1): 3694, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455775

RESUMO

The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We uncover the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. In contrast to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy.


Assuntos
Alquilantes/farmacologia , Bussulfano/farmacologia , Ciclofosfamida/farmacologia , Folículo Piloso/citologia , Regeneração/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Adulto , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Feminino , Folículo Piloso/transplante , Xenoenxertos , Humanos , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco/citologia , Transplante Heterólogo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Cell Prolif ; 52(6): e12672, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31441162

RESUMO

OBJECTIVES: Application of non-invasive imaging methods plays an important role in the assessment of cellular therapy effects in peripheral artery disease. The purpose of this work was to evaluate the kinetics of MRI-derived parameters characterizing ischaemic hindlimb muscle after administration of human mesenchymal stromal cells derived from adipose tissue (hADSC) in mice. MATERIALS AND METHODS: MRI experiments were performed on a 9.4T Bruker system. The measurement protocol included transverse relaxation time mapping and diffusion tensor imaging. The monitoring period encompassed 14 days after femoral artery ligation and subsequent cell administration. The effect of hADSC transplantation was compared with the effect of normal human dermal fibroblasts (NHDFs) and phosphate-buffered saline injection. RESULTS: The most significant differences between the hADSC group and the remaining ones were observed around day 3 after ischaemia induction (increased transverse relaxation time in the hADSC group in comparison with the control group) and around day 7 (increased transverse relaxation time and decreased third eigenvalue of the diffusion tensor in the hADSC group in comparison with the control and NHDF groups) at the site of hADSC injection. Histologically, it was associated with increased macrophage infiltration at days 3-7 and with the presence of small regenerating fibres in the ischaemic tissue at day 7. CONCLUSIONS: Our results underscore the important role of macrophages in mediating the therapeutic effects of hADSCs and confirm the huge potential of magnetic resonance imaging in monitoring of cellular therapy effects.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/fisiologia , Isquemia/patologia , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Imagem de Tensor de Difusão/métodos , Fibroblastos/patologia , Humanos , Masculino , Camundongos Transgênicos , Neovascularização Fisiológica/fisiologia , Regeneração/efeitos dos fármacos , Regeneração/fisiologia
13.
Phytother Res ; 33(11): 2927-2937, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31452263

RESUMO

Curcumin is a dietary polyphenol and a bioactive phytochemical agent that possesses anti-inflammatory, antioxidant, anticancer, and chemopreventive properties. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types. Curcumin protects some stem cells from toxicity and can stimulate proliferation and differentiation of stem cells. In the present review, we summarize the antioxidant, stemness activity, antiaging, and neuroprotective as well as wound healing and regenerative effects of curcumin.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Curcumina/farmacologia , Células-Tronco/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Regeneração/efeitos dos fármacos , Células-Tronco/fisiologia , Cicatrização/efeitos dos fármacos
14.
Gene ; 717: 144047, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31421190

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways play important roles in the formation of the blood vascular system and nervous system across animal phyla. We have earlier reported VEGF and FGF from Hydra vulgaris Ind-Pune, a cnidarian with a defined body axis, an organized nervous system and a remarkable ability of regeneration. We have now identified three more components of VEGF and FGF signaling pathways from hydra. These include FGF-1, FGF receptor 1 (FGFR-1) and VEGF receptor 2 (VEGFR-2) with a view to deciphering their possible roles in regeneration. METHODS: In silico analysis of proteins was performed using Clustal omega, Swiss model, MEGA 7.0, etc. Gene expression was studied by whole mount in situ hybridization. VEGF and FGF signaling was inhibited using specific pharmacological inhibitors and their effects on head regeneration were studied. RESULTS: Expression patterns of the genes indicate a possible interaction between FGF-1 and FGFR-1 and also VEGF and VEGFR-2. Upon treatment of decapitated hydra with pharmacological inhibitor of FGFR-1 or VEGFR-2 for 48 h, head regeneration was delayed in treated as compared to untreated, control regenerates. When we studied the expression of head specific genes HyBra1 and HyKs1 and tentacle specific gene HyAlx in control and treated regenerates using whole mount in situ hybridization, expression of all the three genes was found to be adversely affected in treated regenerates. CONCLUSIONS: The results suggest that VEGF and FGF signaling play important roles in regeneration of hypostome and tentacles in hydra.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Cabeça/fisiologia , Hydra/fisiologia , Regeneração/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Simulação por Computador , Fator 1 de Crescimento de Fibroblastos/química , Fator 1 de Crescimento de Fibroblastos/genética , Fator 1 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Hydra/efeitos dos fármacos , Indóis/farmacologia , Domínios Proteicos , Pirróis/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/química , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Regeneração/efeitos dos fármacos , Transdução de Sinais , Homologia Estrutural de Proteína , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Trials ; 20(1): 469, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366396

RESUMO

BACKGROUND: Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and the production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. METHODS/DESIGN: Based on the SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated-measures design, participants will then receive either placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for eight consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2 and 8 days post exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. DISCUSSION: This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial should provide insight into (1) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and (2) whether skeletal muscle's potential for regeneration depends on its basal SCs content. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03711838 . Registered on 19 Oct 2018.


Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Exercício , Mialgia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Músculo Quadríceps/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Acetilcisteína/efeitos adversos , Adolescente , Adulto , Antioxidantes/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Grécia , Humanos , Masculino , Mialgia/metabolismo , Mialgia/patologia , Oxirredução , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Environ Sci Pollut Res Int ; 26(26): 27435-27443, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327142

RESUMO

Production, distribution, and disposal of pharmaceutical products, including beta-blockers, have become a global issue. Beta-blockers are known to persist in the environment months after their release and may result in the disruption of the homeostatic system in non-target organisms. Here, we study the bioconcentration of three of the most commonly used beta-blockers and their effect on the regeneration of Girardia dorotocephala, a freshwater brown planarian. Acute toxicity tests determined LC50s for acebutolol, metoprolol, and propranolol to be 778 mg/L, 711 mg/L, and 111 mg/L, respectively. The quantification and analysis of beta-blocker bioconcentration during acute exposure were performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After 4 days of exposure to beta-blockers, the bioconcentration drastically decreased for all three beta-blockers at all exposure levels, suggesting that an effective mechanism to reduce uptake or excrete beta-blockers could be present. Additionally, Girardia dorotocephala were cut proximal to the head and the quality of regeneration was documented from each fragment daily. No significant difference was visually observed after 2 weeks of regeneration between the brown planarians placed in beta-blocker solution and those placed in control solution.


Assuntos
Antagonistas Adrenérgicos beta/toxicidade , Planárias/efeitos dos fármacos , Planárias/fisiologia , Regeneração/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antagonistas Adrenérgicos beta/farmacocinética , Animais , Cromatografia Líquida , Ecotoxicologia/métodos , Dose Letal Mediana , Regeneração/fisiologia , Espectrometria de Massas em Tandem , Testes de Toxicidade Aguda , Poluentes Químicos da Água/farmacocinética
17.
Mater Sci Eng C Mater Biol Appl ; 103: 109787, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349479

RESUMO

The purpose of this study is to produce injectable taurine (Tr)-loaded alginate (Agn) hydrogel for age-related macular degeneration (AMD) treatment by inducing the regeneration of RPE (retinal pigment epithelium) cells. Porosity and swelling ratio were measured to evaluate the mechanical properties of the hydrogels, and Fourier transform infrared spectroscopy (FTIR) was used to evaluate the physical and chemical properties. RPE cells extracted from the pigmented epithelium of rabbits were encapsulated in the Tr/Agn hydrogels. Cells proliferation and migration were improved in Tr/Agn hydrogels with an enhanced expression of RPE-specific genes including RPE65, CRALBP, NPR-A, MITF and collagen type I and II. In vivo tests demonstrated the excellent biocompatibility and biodegradability without inflammatory response by the host when implanted with the hydrogel. Moreover, when the Tr/Agn hydrogels were injected into the sub-retinal space, high adhesion of RPE cells and retinal regeneration were confirmed. These results demonstrated a potential role of injectable Tr/Agn hydrogels as potential therapeutic tools for the treatment of retinal diseases, including AMD.


Assuntos
Alginatos/química , Hidrogéis/química , Regeneração , Epitélio Pigmentado da Retina/fisiologia , Taurina/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Força Compressiva , Citocinas/metabolismo , Camundongos Nus , Porosidade , Coelhos , Regeneração/efeitos dos fármacos , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/patologia , Taurina/farmacologia , Engenharia Tecidual
18.
Int J Mol Sci ; 20(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284492

RESUMO

In case of large injuries of skeletal muscles the pool of endogenous stem cells, i.e., satellite cells, might be not sufficient to secure proper regeneration. Such failure in reconstruction is often associated with loss of muscle mass and excessive formation of connective tissue. Therapies aiming to improve skeletal muscle regeneration and prevent fibrosis may rely on the transplantation of different types of stem cell. Among such cells are adipose tissue-derived stromal cells (ADSCs) which are relatively easy to isolate, culture, and manipulate. Our study aimed to verify applicability of ADSCs in the therapies of severely injured skeletal muscles. We tested whether 3D structures obtained from Matrigel populated with ADSCs and transplanted to regenerating mouse gastrocnemius muscles could improve the regeneration. In addition, ADSCs used in this study were pretreated with myoblasts-conditioned medium or anti-TGFß antibody, i.e., the factors modifying their ability to proliferate, migrate, or differentiate. Analyses performed one week after injury allowed us to show the impact of 3D cultured control and pretreated ADSCs at muscle mass and structure, as well as fibrosis development immune response of the injured muscle.


Assuntos
Tecido Adiposo/citologia , Colágeno/farmacologia , Laminina/farmacologia , Músculo Esquelético/patologia , Proteoglicanas/farmacologia , Regeneração/efeitos dos fármacos , Animais , Anticorpos/farmacologia , Forma Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Combinação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Células Estromais/transplante , Fator de Crescimento Transformador beta/metabolismo
19.
Chemosphere ; 233: 273-281, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31176128

RESUMO

Chlorine plays a primary role in the disinfection of drinking water and wastewater due to its effectiveness as a biocide; however, there is evidence of the formation of toxic byproducts from its application, and this has promoted the search for alternatives. Alternative disinfectants can be effective in the inactivation of pathogenic microorganisms and are less damaging to human health and aquatic ecosystems. However, more information is needed on the effect of residual concentrations on the environment. This work compares the ecotoxicological effects of PAA disinfectants and the active chlorine of calcium hypochlorite in relation to the organism Dugesia tigrina (planaria), in terms of the acute effects: LC50, and chronic effects: feeding, locomotion, regeneration, reproduction and fertility. The results indicated that the active chlorine was more toxic than PAA, with LC50 (96 h) of 2.63 mg.L-1 and 3.16 mg.L-1, respectively. Sub-lethal exposure to active chlorine was more toxic when compared to PAA, and there was evidence of significantly reduced feeding and locomotion, causing a greater delay in regeneration and impairment in reproduction and fertility. The results allowed the comparison of the two disinfectants using half-life constants of the compounds and the lowest observed effect level (LOEC) of the oxidants. Chlorine represents a greater risk to the ecosystem for a longer period. The results obtained in this study can help in the establishment of discharge limits for PAA in water bodies.


Assuntos
Cloro/toxicidade , Desinfetantes/toxicidade , Ecotoxicologia/métodos , Ácido Peracético/toxicidade , Planárias/efeitos dos fármacos , Animais , Compostos de Cálcio/química , Desinfecção/métodos , Biomarcadores Ambientais/efeitos dos fármacos , Feminino , Fertilidade , Planárias/fisiologia , Regeneração/efeitos dos fármacos , Águas Residuárias/química , Poluentes Químicos da Água/toxicidade
20.
Biofabrication ; 11(4): 044101, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151123

RESUMO

Osteochondral (OC) tissue is a biphasic material comprised of articular cartilage integrated atop subchondral bone. Damage to this tissue is highly problematic, owing to its intrinsic inability to regenerate functional tissue in response to trauma or disease. Further, the function of the tissue is largely conferred by its compartmentalized zonal microstructure and composition. Current clinical treatments fail to regenerate new tissue that recapitulates this zonal structure. Consequently, regenerated tissue often lacks long-term stability. To address this growing problem, we propose the development of tissue engineered biomaterials that mimic the zonal cartilage organization and extracellular matrix composition through the use of a microfluidic printing head bearing a mixing unit and incorporated into an extrusion-based bioprinter. The system is devised so that multiple bioinks can be delivered either individually or at the same time and rapidly mixed to the extrusion head, and finally deposited through a coaxial nozzle. This enables the deposition of either layers or continuous gradients of chemical, mechanical and biological cues and fabrication of scaffolds with very high shape fidelity and cell viability. Using such a system we bioprinted cell-laden hydrogel constructs recapitulating the layered structure of cartilage, namely, hyaline and calcified cartilage. The construct was assembled out of two bioinks specifically formulated to mimic the extracellular matrices present in the targeted tissues and to ensure the desired biological response of human bone marrow-derived mesenchymal stem cells and human articular chondrocytes. Homogeneous and gradient constructs were thoroughly characterized in vitro with respect to long-term cell viability and expression of hyaline and hypertrophic markers by means of real-time quantitative PCR and immunocytochemical staining. After 21 days of in vitro culture, we observed production of zone-specific matrix. The PCR analysis demonstrated upregulated expression of hypertrophic markers in the homogenous equivalent of calcified cartilage but not in the gradient heterogeneous construct. The regenerative potential was assessed in vivo in a rat model. The histological analysis of surgically damaged rat trochlea revealed beneficial effect of the bioprinted scaffolds on regeneration of OC defect when compared to untreated control.


Assuntos
Bioimpressão , Cartilagem Articular/patologia , Hidrogéis/farmacologia , Microfluídica/instrumentação , Impressão Tridimensional , Regeneração , Animais , Cartilagem Articular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Humanos , Implantes Experimentais , Tinta , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos Wistar , Regeneração/efeitos dos fármacos
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