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1.
Biomater Adv ; 159: 213837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522310

RESUMO

Poloxamer-based hydrogels show promise to stabilise and sustain the delivery of growth factors in tissue engineering applications, such as following spinal cord injury. Typically, growth factors such as neurotrophin-3 (NT-3) degrade rapidly in solution. Similarly, poloxamer hydrogels also degrade readily and are, therefore, only capable of sustaining the release of a payload over a small number of days. In this study, we focused on optimising a hydrogel formulation, incorporating both poloxamer 188 and 407, for the sustained delivery of bioactive NT-3. Hyaluronic acid blended into the hydrogels significantly reduced the degradation of the gel. We identified an optimal hydrogel composition consisting of 20 % w/w poloxamer 407, 5 % w/w poloxamer 188, 0.6 % w/w NaCl, and 1.5 % w/w hyaluronic acid. Heparin was chemically bound to the poloxamer chains to enhance interactions between the hydrogel and the growth factor. The unmodified and heparin-modified hydrogels exhibited sustained release of NT-3 for 28 days while preserving the bioactivity of NT-3. Moreover, these hydrogels demonstrated excellent cytocompatibility and had properties suitable for injection into the intrathecal space, underscoring their suitability as a growth factor delivery system. The findings presented here contribute valuable insights to the development of effective delivery strategies for therapeutic growth factors for tissue engineering approaches, including the treatment of spinal cord injury.


Assuntos
Hidrogéis , Traumatismos da Medula Espinal , Humanos , Hidrogéis/uso terapêutico , Poloxâmero/química , Poloxâmero/uso terapêutico , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/uso terapêutico , Ácido Hialurônico/química , Ácido Hialurônico/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Heparina/farmacologia , Heparina/química , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
2.
Cells ; 13(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38474373

RESUMO

The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.


Assuntos
Glioblastoma , Células-Tronco Neoplásicas , Sirolimo , Humanos , Glioblastoma/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Células-Tronco Neoplásicas/metabolismo
3.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338805

RESUMO

Platelet concentrates such as platelet-rich plasma, platelet-rich fibrin or concentrated growth factors are cost-effective autologous preparations containing various growth factors, including platelet-derived growth factor, transforming growth factor ß, insulin-like growth factor 1 and vascular endothelial growth factor. For this reason, they are often used in regenerative medicine to treat wounds, nerve damage as well as cartilage and bone defects. Unfortunately, after administration, these preparations release growth factors very quickly, which lose their activity rapidly. As a consequence, this results in the need to repeat the therapy, which is associated with additional pain and discomfort for the patient. Recent research shows that combining platelet concentrates with biomaterials overcomes this problem because growth factors are released in a more sustainable manner. Moreover, this concept fits into the latest trends in tissue engineering, which include biomaterials, bioactive factors and cells. Therefore, this review presents the latest literature reports on the properties of biomaterials enriched with platelet concentrates for applications in skin, nerve, cartilage and bone tissue engineering.


Assuntos
Plasma Rico em Plaquetas , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Materiais Biocompatíveis/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Medicina Regenerativa/métodos , Fator de Crescimento Derivado de Plaquetas , Plasma Rico em Plaquetas/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Plaquetas/fisiologia
4.
J Wound Care ; 33(Sup2a): x-xiii, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324424

RESUMO

Treatment of soft tissue wounds with bone or tendon exposure remains a tough clinical challenge for surgeons. The current clinical approaches include various types of flap reconstruction and artificial dermis grafting as well as negative pressure wound therapy (NPWT), which are time-consuming and often result in graft failure or significant scarring. Concentrated growth factor (CGF) is a novel blood extract that contains many growth factors, platelets and fibrin to promote an orderly healing process. However, few reports have focused on wounds with bone or tendon exposure. We present a limited series and two specific cases of skin wound with bone or tendon exposed that received surgical debridement followed by CGF treatment. CGF appeared to facilitate wound closure effectively and also reduced scar formation. Our findings provide a novel therapeutic option for refractory wounds with bone or tendon exposure.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Lesões dos Tecidos Moles , Humanos , Transplante de Pele , Cicatrização , Lesões dos Tecidos Moles/terapia , Cicatriz/cirurgia , Tendões/cirurgia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Resultado do Tratamento
5.
Parasit Vectors ; 17(1): 46, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303078

RESUMO

BACKGROUND: Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI. METHODS: Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism. RESULTS: Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1ß). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1ß and 4-HNE in the iRBC-stimulated Raw264.7 cells. CONCLUSIONS: Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI.


Assuntos
Lesão Pulmonar Aguda , Peptídeos e Proteínas de Sinalização Intercelular , Canais Iônicos , Malária Cerebral , Venenos de Aranha , Animais , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/parasitologia , Citocinas/genética , Citocinas/metabolismo , Interleucina-10/metabolismo , Interleucina-4 , Canais Iônicos/antagonistas & inibidores , Lipopolissacarídeos , Pulmão/parasitologia , Malária Cerebral/complicações , Malária Cerebral/tratamento farmacológico , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Venenos de Aranha/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
6.
Am J Sports Med ; 52(1): 242-257, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38164688

RESUMO

Orthobiologics are rapidly growing in use given their potential to augment healing for multiple musculoskeletal conditions. Orthobiologics consist of a variety of treatments including platelet-rich plasma and stem cells that provide conceptual appeal in providing local delivery of growth factors and inflammation modulation. The lack of standardization in nomenclature and applications within the literature has led to a paucity of high-quality evidence to support their frequent use. The purpose of this review was to describe the current landscape of orthobiologics and the most recent evidence regarding their use.


Assuntos
Doenças Musculoesqueléticas , Plasma Rico em Plaquetas , Humanos , Doenças Musculoesqueléticas/terapia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
7.
Spinal Cord ; 62(1): 17-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38001173

RESUMO

STUDY DESIGN: Preclinical pharmacology. OBJECTIVES: Our study aims to evaluate the combined effect of Methylprednisolone (MP) and growth factor-rich serum (GFRS) on structural and functional recovery in rats following spinal cord injury (SCI). SETTING: Shiraz University of Medical Sciences, Shiraz, Iran METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: sham group (laminectomy); SCI group (the spinal cord clip compression model); SCI-MP group (30 mg/kg MP was administrated intraperitoneally (IP) immediately after SCI); SCI-GFRS group (GFRS (200 µl, IP) was administrated for six consecutive days); and SCI-MP + GFRS group (the rats received MP (30 mg/kg, IP) immediately after SCI, and GFRS (200 µl, IP) for six consecutive days). Motor function was assessed weekly using the Basso, Beattie, and Bresnahan (BBB) scale. After 4 weeks, we conducted the rotarod test, then removed and prepared the spinal cords (including the epicenter of injury) for stereological and histological estimation, and biochemical assays. RESULTS: The results showed that MP and GFRS combining treatment enhanced functional recovery, which was associated with a decrement in lesion volume, increased spared white and gray matter volume, reduced neuronal loss, as well as decreased necrosis and hemorrhage after SCI. Moreover, administration of MP and GFRS inhibited lipid peroxidation (malondialdehyde (MDA) content), and increased antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) after rat SCI. CONCLUSIONS: We suggests that the combination treatment of MP and GFRS may ameliorate the structure and functional changes following SCI by reducing oxidative stress, and increasing the level of antioxidants enzymes.


Assuntos
Fármacos Neuroprotetores , Compressão da Medula Espinal , Traumatismos da Medula Espinal , Ratos , Masculino , Animais , Metilprednisolona/uso terapêutico , Ratos Sprague-Dawley , Fármacos Neuroprotetores/farmacologia , Medula Espinal/patologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
8.
Facial Plast Surg ; 40(1): 112-119, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36423628

RESUMO

Concentrated growth factor (CGF), which is a third-generation platelet concentrate product, exhibits good potential for repair and regeneration of soft and hard tissues, and has gradually attracted attention in the field of cosmetic plastic surgery. The purpose of this review is to summarize the application and research of CGF in the field of facial rejuvenation and plastic surgery. A comprehensive review of the literature about the applications of CGF in facial rejuvenation and plastic surgery was conducted in PubMed, Ovid MEDLINE, and Web of Science. According to the inclusion and exclusion criteria, a total of 22 articles were included in this review. In recent years, CGF has been applied in many aspects in the field of facial rejuvenation and plastic surgery, including skin photoaging, repairment of soft-tissue defects, rhinoplasty, hair loss, autologous fat transplantation, and scars. In addition, no significant adverse reactions have been reported so far. CGF is rich in high-concentration growth factors, which has great potential and application prospects in facial rejuvenation and plastic surgery. However, the applications of CGF still have some problems, such as the mechanism, time of decomposition, and long-term efficacy and safety, which are needed to be resolved in future.


Assuntos
Técnicas Cosméticas , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Humanos , Rejuvenescimento , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
9.
J Theor Biol ; 576: 111652, 2024 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-37952610

RESUMO

Multiple myeloma (MM) is a genetically complex hematological cancer characterized by the abnormal proliferation of malignant plasma cells in the bone marrow. This disease progresses from a premalignant condition known as monoclonal gammopathy of unknown significance (MGUS) through sequential genetic alterations involving various genes. These genetic changes contribute to the uncontrolled growth of multiple clones of plasma cells. In this study, we present a phenotype-structured model that captures the intra-clonal heterogeneity and drug resistance in multiple myeloma (MM). The model accurately reproduces the branching evolutionary pattern observed in MM progression, aligning with a previously developed multiscale model. Numerical simulations reveal that higher mutation rates enhance tumor phenotype diversity, while access to growth factors accelerates tumor evolution and increases its final size. Interestingly, the model suggests that further increasing growth factor access primarily amplifies tumor size rather than altering clonal dynamics. Additionally, the model emphasizes that higher mutation frequencies and growth factor availability elevate the chances of drug resistance and relapse. It indicates that the timing of the treatment could trajectory of tumor evolution and clonal emergence in the case of branching evolutionary pattern. Given its low computational cost, our model is well-suited for quantitative studies on MM clonal heterogeneity and its interaction with chemotherapeutic treatments.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Gamopatia Monoclonal de Significância Indeterminada/genética , Gamopatia Monoclonal de Significância Indeterminada/patologia , Células Clonais , Resistência a Medicamentos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
10.
Curr Probl Cardiol ; 49(1 Pt B): 102088, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37716542

RESUMO

Vascular disease is a common problem with high mortality all over the world. Apelin-13, a key subtype of apelin, takes part in many physiological and pathological responses via regulating many target genes and target molecules or participating in many signaling pathways. More and more studies have demonstrated that apelin-13 is implicated in the onset and progression of vascular disease in recent years. It has been shown that apelin-13 could ameliorate vascular disease by inhibiting inflammation, restraining apoptosis, suppressing oxidative stress, and facilitating autophagy. In this article, we sum up the progress of apelin-13 in the occurrence and development of vascular disease and offer some insightful views about the treatment and prevention strategies of vascular disease.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Doenças Vasculares , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Doenças Vasculares/prevenção & controle
11.
ACS Biomater Sci Eng ; 9(12): 6531-6547, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37968925

RESUMO

The controlled delivery of growth factors (GFs) from tissue engineered constructs represents a promising strategy to improve tissue repair and regeneration. However, despite their established key role in tissue regeneration, the use of GFs is limited by their short half-life in the in vivo environment, their dose-dependent effectiveness, and their space- and time-dependent activity. Promising results have been obtained both in vitro and in vivo in animal models. Nevertheless, the clinical application of tissue engineered constructs releasing GFs is still challenging due to the several limitations and risks associated with their use. 3D printing and bioprinting, by allowing the microprecise spatial deposition of multiple materials and the fabrication of complex geometries with high resolution, offer advanced strategies for an optimal release of GFs from tissue engineered constructs. This review summarizes the strategies that have been employed to include GFs and their delivery system into biomaterials used for 3D printing applications to optimize their controlled release and to improve both the in vitro and in vivo regeneration processes. The approaches adopted to overcome the above-mentioned limitations are presented, showing the potential of the technology of 3D printing to get one step closer to clinical applications.


Assuntos
Bioimpressão , Engenharia Tecidual , Animais , Engenharia Tecidual/métodos , Materiais Biocompatíveis/uso terapêutico , Impressão Tridimensional , Bioimpressão/métodos , Cicatrização , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
12.
BMC Oral Health ; 23(1): 821, 2023 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-37899448

RESUMO

BACKGROUND: This randomized controlled clinical trial compared the effects of platelet-rich fibrin (PRF) and concentrated growth factor (CGF) on early bone healing after endodontic microsurgery. METHODS: Eighteen patients with an isolated periapical lesion < 10 mm in the maxillary anterior region were randomly assigned to three groups: control, PRF, or CGF. Endodontic microsurgery was performed and PRF or CGF membranes were placed over the bone defects in the experimental groups. The volume of the bone defect at postoperative one week, three months, and six months was evaluated using cone-beam computed tomography and Mimics software. The results were statistically analyzed using the Kruskal-Wallis test and post-hoc Mann-Whitney U test with Bonferroni correction. RESULTS: At the three-month follow-up, the PRF and CGF groups showed significantly greater bone healing compared with the control group (p > 0.05). However, no significant difference was observed between the PRF and CGF groups. At the six-month follow-up, no significant differences were observed between the groups. CONCLUSIONS: These results suggested that PRF and CGF promote early bone healing after endodontic microsurgery.


Assuntos
Fibrina Rica em Plaquetas , Humanos , Fibrina Rica em Plaquetas/metabolismo , Microcirurgia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Tomografia Computadorizada de Feixe Cônico/métodos
13.
BMC Oral Health ; 23(1): 712, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794381

RESUMO

BACKGROUND: Concentrated growth factor (CGF), a new autologous platelet concentrate, has been widely investigated to the adjunctive treatment of oral diseases. This study aims to evaluate the efficacy of CGF in the surgical treatment of oral diseases. METHODS: MEDLINE, Web of Science, Scopus, Cochrane, and EMBASE databases were searched up to July 2023. Only randomized clinical trials were included. The methodologic quality was evaluated by the Cochrane Risk of Bias Tool. RevMan 5.4 software was used for data analysis. RESULTS: In the treatment of periodontal intrabony defects, bone graft combined with CGF was significantly superior to bone graft (P < 0.01), with mean intrabony defect depth reduction of 1.41 mm and mean clinical attachment level gain of 0.55 mm. In the regenerative surgery of furcation defects, the effect of CGF group was significantly better than control group (P < 0.0001), with mean probing depth reduction of 0.99 mm, vertical bone gain of 0.25 mm, and horizontal bone gain of 0.34 mm. CGF combined with coronally advanced flap (CAF) was more effective than CAF alone (mean keratinized tissue width increase of 0.41 mm, mean gingival thickness increase of 0.26 mm, P < 0.00001), but less effective than connective tissue graft (CTG) combined with CAF (mean root coverage difference of -15.1%, mean gingival thickness difference of -0.5 mm, P < 0.0001). In the alveolar ridge preservation, additional use of CGF reduced horizontal bone resorption by 1.41 mm and buccal vertical bone resorption by 1.01 mm compared to control group (P < 0.0001). The VAS score of CGF group was significantly lower than that of the control group at the 1st and 7th day after oral surgery (P < 0.0001). CONCLUSIONS: CGF can exert a positive adjunctive effect for the regenerative surgery of periodontal intrabony defects, furcation defects, and alveolar ridge preservation procedure. CGF combined with CAF has a better therapeutic effect on gingival recession compared to CAF alone, although it is not as effective as CTG combined with CAF. CGF could promote postoperative healing and pain relief in oral surgery within a week. There is currently not enough evidence to support the clinical benefits of CGF in other oral surgeries.


Assuntos
Reabsorção Óssea , Defeitos da Furca , Retração Gengival , Humanos , Retalhos Cirúrgicos/transplante , Retração Gengival/cirurgia , Gengiva , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Resultado do Tratamento , Raiz Dentária/cirurgia
14.
Rheum Dis Clin North Am ; 49(4): 773-787, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821195

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic vasculitis syndrome caused by biallelic mutations in the adenosine deaminase 2 gene. The diagnosis of DADA2 is confirmed by decreased enzymatic activity of ADA2 and genetic testing. Symptoms range from cutaneous vasculitis and polyarteritis nodosa-like lesions to stroke. The vasculopathy of DADA2 can affect many organ systems, including the gastrointestinal and renal systems. Hematologic manifestations occur early with hypogammaglobulinemia, lymphopenia, pure red cell aplasia, or pancytopenia. Treatment can be challenging. Tumor necrosis factor inhibitors are helpful to control inflammatory symptoms. Hematopoietic stem cell transplant may be needed to treat refractory cytopenias, vasculopathy, or immunodeficiency.


Assuntos
Poliarterite Nodosa , Vasculite , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Poliarterite Nodosa/complicações , Mutação
15.
Heart Lung Circ ; 32(7): 798-807, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37407301

RESUMO

Ischaemic heart disease is the primary cause of death worldwide with myocardial infarction (MI) contributing to significant morbidity and mortality. The human heart has a limited capacity to regenerate and the significant loss of cardiomyocytes after MI can overwhelm this limited innate regenerative capability. This is in part compensated for by the creation of collagen-rich scar tissue. Therapeutic angiogenesis is an exciting prospect that can assist cardiac regeneration after MI with various approaches having been explored. This review will focus on results from clinical growth factor trials, and the lack of clinical translation. Inconsistencies in results from these may be due to heterogeneity within patient selection and an incomplete understanding of therapeutic differences between isoforms of active agents. The technology used has also evolved with recombinant protein and, subsequently, gene therapy being utilised. Innovative therapeutic designs, such as combinatorial therapies, might help to resolve these issues in the future.


Assuntos
Infarto do Miocárdio , Humanos , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Miócitos Cardíacos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Terapia Genética
16.
Rom J Ophthalmol ; 67(2): 185-190, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37522013

RESUMO

The pattern dystrophies (PDs) are a group of primarily autosomal dominant inherited macular diseases that cause the deposition of lipofuscin in retinal pigment epithelium (RPE) and may lead to significant vision loss in later life. Patients can develop choroidal neovascularization (CNV) and/ or geographic atrophy (GA) and for this reason they are often misdiagnosed as age-related macular degeneration (AMD). We presented a case of a 66-year-old patient complaining of vision loss in the right eye (RE) for 8 months. At the initial examination, his best corrected visual acuity (BCVA) was 0.6 in the RE. Optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) allowed to diagnose butterfly-shaped PD in both eyes with choroidal neovascularization (CNV) in the RE. The patient was treated with three intravitreal anti-vascular epithelial growth factor (anti-VEGF, ranibizumab) injections during six weeks intervals, which improved and stabilized the BCVA of the RE to 0.7 during the over two-year observation period. Our report contributes to the still limited data regarding CNV associated with butterfly-shaped PDs and the results of treatment with ranibizumab. Abbreviations: AMD = age-related macular degeneration, anti-VEGF = anti-vascular epithelial growth factor, AOFVD = adult-onset foveomacular vitelliform dystrophy, BCVA = best corrected visual acuity, CNV = choroidal neovascularization, FAF = fundus autofluorescence, FFA = fundus fluorescein angiography, GA = geographic atrophy, LE = left eye, MIDD = maternally inherited diabetes and deafness, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, OU = oculus uterque, both eyes, PD = pattern dystrophy, PDSFF = pattern dystrophy simulating fundus flavimaculatus, PDT = photodynamic therapy, PRPH2 = peripherine-2, RE = right eye, RPE = retinal pigment epithelium, VA = visual acuity.


Assuntos
Neovascularização de Coroide , Anormalidades do Olho , Atrofia Geográfica , Distrofia Macular Viteliforme , Adulto , Humanos , Idoso , Ranibizumab , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Distrofia Macular Viteliforme/complicações , Distrofia Macular Viteliforme/diagnóstico , Distrofia Macular Viteliforme/tratamento farmacológico , Tomografia de Coerência Óptica , Angiofluoresceinografia , Anormalidades do Olho/complicações , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Injeções Intravítreas , Inibidores da Angiogênese/uso terapêutico
17.
BMC Oral Health ; 23(1): 482, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452298

RESUMO

BACKGROUND: The aim of this retrospective study was to compare the efficacy of concentrated growth factor (CGF) and platelet-rich fibrin (PRF) as scaffolds in regenerative endodontic therapy (RET). METHODS: Necrotic immature permanent teeth treated with regenerative endodontic therapy during January 2018 to August 2022 were divided into the CGF and PRF groups according to the scaffold. The CGF and PRF groups included 7 and 6 teeth, respectively. The efficacy of regenerative endodontic therapy was analyzed based on the clinical and radiological outcomes at three different follow up periods: T1 (3-6 months), T2 (6-12 months) and T3 (12-24 months). Statistical analysis was performed using the independent T test, Mann-Whitney test and Fisher's exact test at a significance level of 0.05. RESULTS: The success rate of each stage in both groups was 100%. Through quantitative comparison of radiographic outcomes, there was no statistically significant difference between the two groups in terms of root development and periapical lesion healing at each stage, except that the increase rate of radiographic root area in PRF group in the T3 stage was above one in CGF group with statistically significance. CONCLUSIONS: Both CGF and PRF had a similar clinical performance regarding resolution of clinical signs and symptoms, periapical lesion healing, and continued root development as scaffolds in RET. Further prospective studies with large samples for longer follow-up periods are needed.


Assuntos
Fibrina Rica em Plaquetas , Endodontia Regenerativa , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
18.
Diabetes Metab Res Rev ; 39(5): e3670, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37277960

RESUMO

INTRODUCTION: This study examined the relative efficacy of growth factor therapies in healing diabetes-related foot ulcers (DFU). METHODS: PubMed and Cochrane databases were searched for randomized controlled trials testing growth factor therapies for treating DFU. The primary outcome was complete wound closure. Results were reported as relative risk (RR) ± 95% credible intervals (CrI). The risk of bias was assessed using Cochrane's RoB-2 tool. RESULTS: A total of 31 RCTs involving 2174 participants were included. Only 13 of the trials (n = 924) reported on the aetiology of the ulcers (85.4% neuropathic and 14.6% ischaemic). Epidermal growth factor (RR 3.83; 95% CrI 1.81, 9.10), plasma-rich protein (PRP) (RR 3.36; 95% CrI 1.66, 8.03) and platelet-derived growth factor (PDGF) (RR 2.47; 95% CrI 1.23, 5.17) significantly improved the likelihood of complete ulcer healing compared to control. Sub-analyses suggested that PRP (3 trials - RR 9.69; 95% CrI 1.37, 103.37) and PDGF (6 trials - RR 2.22; 95% CrI 1.12, 5.19) significantly improved the likelihood of wound closure amongst trial mainly recruiting participants with neuropathic ulcers. Eleven trials had a low risk of bias, 9 had some concerns and 11 had a high risk of bias. Sub-analysis of trials with a low risk of bias suggested that none of the growth factors significantly improved ulcer healing compared with control. DISCUSSION: This network meta-analysis found low-quality evidence that Epidermal growth factor, PRP and PDGF therapy improved DFU healing likelihood compared with control. Larger well-designed trials are needed.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/tratamento farmacológico , Pé Diabético/etiologia , Úlcera , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Família de Proteínas EGF
19.
Biomolecules ; 13(5)2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37238679

RESUMO

The use of biomaterials and bioactive agents has shown promise in bone defect repair, leading to the development of strategies for bone regeneration. Various artificial membranes, especially collagen membranes (CMs) that are widely used for periodontal therapy and provide an extracellular matrix-simulating environment, play a significant role in promoting bone regeneration. In addition, numerous growth factors (GFs) have been used as clinical applications in regenerative therapy. However, it has been established that the unregulated administration of these factors may not work to their full regenerative potential and could also trigger unfavorable side effects. The utilization of these factors in clinical settings is still restricted due to the lack of effective delivery systems and biomaterial carriers. Hence, considering the efficiency of bone regeneration, both spaces maintained using CMs and GFs can synergistically create successful outcomes in bone tissue engineering. Therefore, recent studies have demonstrated a significant interest in the potential of combining CMs and GFs to effectively promote bone repair. This approach holds great promise and has become a focal point in our research. The purpose of this review is to highlight the role of CMs containing GFs in the regeneration of bone tissue, and to discuss their use in preclinical animal models of regeneration. Additionally, the review addresses potential concerns and suggests future research directions for growth factor therapy in the field of regenerative science.


Assuntos
Regeneração Óssea , Colágeno , Animais , Osso e Ossos , Cicatrização , Engenharia Tecidual , Materiais Biocompatíveis/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
20.
J Endod ; 49(7): 836-845, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37182792

RESUMO

INTRODUCTION: Concentrated growth factor (CGF) is the third-generation platelet concentrate product. This study aimed to evaluate whether the use of CGF during endodontic microsurgery had a positive influence on surgical outcomes. METHODS: Fifty-four patients who underwent endodontic microsurgery from January 2017 to November 2021 were enrolled. They were assigned to the CGF and the control groups according to whether CGF was used during the surgery and followed up at 6, 12, and 18 months after surgery. Preoperative classification of the cases and follow-up radiographic outcomes were based on Kim's classification and Molven's criteria, respectively, and evaluated by 2 calibrated endodontists. The Student t test and χ2 test were used to assess the baseline of 2 groups. Rank sum test was used to determine whether CGF had an impact on the surgical outcome. RESULTS: Thirty-one patients (41 periapical lesion sites) were included in the CGF group, and 23 patients (26 periapical lesion sites) were included in the control group. The overall success rate of endodontic microsurgery was greater than 90%. The baseline of the 2 groups had no difference (P < .05). In the CGF group, the success rate was always 100% in 3 follow-ups, whereas the success rate was 84.2%, 92.8%, and 90%, respectively, in the control group. The success rate between the CGF group and the control group was statistically significant in all 3 follow-up points (P < .05). CONCLUSIONS: The application of CGF during endodontic microsurgery might have a positive influence on surgical outcomes, thus, its prognosis. However, higher-grade evidence is needed to demonstrate its role.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Microcirurgia , Humanos , Resultado do Tratamento , Estudos Transversais , Prognóstico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
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