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1.
Comput Stand Interfaces ; 83: 103643, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35400843

RESUMO

The COVID-19 pandemic has severely affected daily life and caused a great loss to the global economy. Due to the very urgent need for identifying close contacts of confirmed patients in the current situation, the development of automated contact tracing app for smart devices has attracted more attention all over the world. Compared with expensive manual tracing approach, automated contact tracing apps can offer fast and precise tracing service, however, over-pursing high efficiency would lead to the privacy-leaking issue for app users. By combing with the benign properties (e.g., anonymity, decentralization, and traceability) of blockchain, we propose an efficient privacy-preserving solution in automated tracing scenario. Our main technique is a combination of non-interactive zero-knowledge proof and multi-signature with public key aggregation. By means of aggregating multiple signatures from different contacts at the mutual commitment phase, we only need fewer zero-knowledge proofs to complete the task of identifying contacts. It inherently leads to the benefits of saving storage and consuming less time for running verification algorithm on blockchain. Furthermore, we perform an experimental comparison by timing the execution of signature verification with and without aggregate signature, respectively. It shows that our solution can actually preserve the full-fledged privacy protection property with a lower computational cost.

2.
Bioact Mater ; 19: 24-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35415312

RESUMO

Wound healing is a highly orchestrated process involving a variety of cells, including immune cells. Developing immunomodulatory biomaterials for regenerative engineering applications, such as bone regeneration, is an appealing strategy. Herein, inspired by the immunomodulatory effects of gastrodin (a bioactive component in traditional Chinese herbal medicine), a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane (gastrodin-PU) and nano-hydroxyapatite (n-HA) (gastrodin-PU/n-HA) composites were developed. RAW 264.7 macrophages, rat bone marrow mesenchymal stem cells (rBMSCs), and human umbilical vein endothelial cells (HUVECs) were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin (0.5%, 1%, and 2%) to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro. Results demonstrated that, compared with PU/n-HA, gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype, as evidenced by the higher expression level of pro-regenerative cytokines (CD206, Arg-1) and the lower expression of pro-inflammatory cytokines (iNOS). The expression levels of osteogenesis-related factors (BMP-2 and ALP) in the rBMSCs and angiogenesis-related factors (VEGF and BFGF) in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium. The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory (M1) phenotype to an anti-inflammatory and pro-healing (M2) phenotype were validated in a rat subcutaneous implantation model. And the 2% gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis. Additionally, 2% gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis. Thus, the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.

3.
Bioact Mater ; 19: 12-23, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35415313

RESUMO

Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures. Biodegradable Zn metals are revolutionary materials for orthopedic implants. In this study, pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion (L-PBF) technology. First, the mechanical properties, corrosion behavior, and biocompatibility of the pure Zn porous scaffolds were characterized in vitro. The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks. The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone, as well as relatively suitable degradation rates for bone regeneration. A benign host response was observed using hematoxylin and eosin (HE) staining of the heart, liver, spleen, lungs, and kidneys. Moreover, the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo. This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.

4.
Bioact Mater ; 19: 38-49, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35415314

RESUMO

Ischemic stroke is an acute and serious cerebral vascular disease, which greatly affects people's health and brings huge economic burden to society. Microglia, as important innate immune components in central nervous system (CNS), are double-edged swords in the battle of nerve injury, considering their polarization between pro-inflammatory M1 or anti-inflammatory M2 phenotypes. High mobility group box 1 (HMGB1) is one of the potent pro-inflammatory mediators that promotes the M1 polarization of microglia. 18ß-glycyrrhetinic acid (GA) is an effective intracellular inhibitor of HMGB1, but of poor water solubility and dose-dependent toxicity. To overcome the shortcomings of GA delivery and to improve the efficacy of cerebral ischemia therapy, herein, we designed reactive oxygen species (ROS) responsive polymer-drug conjugate nanoparticles (DGA) to manipulate microglia polarization by suppressing the translocation of nuclear HMGB1. DGA presented excellent therapeutic efficacy in stroke mice, as evidenced by the reduction of infarct volume, recovery of motor function, suppressed of M1 microglia activation and enhanced M2 activation, and induction of neurogenesis. Altogether, our work demonstrates a close association between HMGB1 and microglia polarization, suggesting potential strategies for coping with inflammatory microglia-related diseases.

5.
Bioact Mater ; 19: 1-11, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35415315

RESUMO

The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours. Ferroptosis, resulting from the iron-dependent accumulation of lipid peroxides, has the potential to reverse multidrug resistance. However, simultaneous delivery of the iron sources, ferroptosis inducers, drugs, and enhanced circulation carriers within matrices remains a significant challenge. Herein, we designed and fabricated a defect self-assembly of metal-organic framework (MOF)-red blood cell (RBC) membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer. Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron (III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process. The RBC membrane could camouflage the nanoplatform for longer circulation. Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione, amplify the reactive oxidative species oxidative stress, and enable remarkable anticancer properties. Our work provides an alternative strategy for overcoming multidrug resistance, which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis. This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.

6.
Bioact Mater ; 19: 103-114, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35441115

RESUMO

Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone. At 12 months, large amounts of bone (∼75%) occupy the hollow space with strong evidence of ongoing remodelling. Features of both compact bone (osteonal/osteon-like arrangements) and spongy bone (trabeculae separated by marrow cavities) reveal insights into function/need-driven microstructural adaptation. Pores within the CaP also contain both woven bone and vascularised lamellar bone. Osteoclasts actively contribute to CaP degradation/removal. Of the constituent phases, only calcium pyrophosphate persists within osseous (cutting cones) and non-osseous (macrophages) sites. From a translational perspective, this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.

7.
Bioact Mater ; 19: 88-102, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35441114

RESUMO

Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice. Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface, graft necrosis and sclerosis. However, poor gap integration is a serious concern, which eventually leads to deterioration of joint function. To deal with such complications, this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl (GelMA) hydrogel (BSN-GelMA). A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty, as early as six weeks. Moreover, the International Cartilage Repair Society score, histology score, glycosaminoglycan content, subchondral bone volume, and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group. This improved outcome was due to bio-interactive materials, which acted as tissue fillers to bridge the gap, prevent cartilage degeneration, and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel. This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty. It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.

8.
Bioact Mater ; 20: 355-367, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784635

RESUMO

Infection and healing of wounds after injury has always been an unavoidable problem in daily life, so design of a biomaterial with antibacterial and good wound healing properties is highly needed. Herein, a wound healing hydrogel dressing with halloysite clay and chitin as the main components was prepared, which combines the advantages of the biomacromolecule and clay. Halloysite nanotubes (HNTs) are extremely biocompatible clay materials with a hollow tubular structure, and the inner and outer surfaces of HNTs are composed of SiOx and AlOx layers with different charges. Au nanoparticles with diameter in 5-10 nm were filled into the HNTs' lumen to endow photothermal effect of the clay materials. Au@HNTs was then mixed with chitin solution to prepare flexible composite hydrogel by crosslinking by epichlorohydrin. The antibacterial properties, biocompatibility and hemostatic properties of the hydrogel material were investigated by antibacterial experiments, cell experiments, mouse liver and tail hemostatic experiments. After infecting the back wound of mice with Staphylococcus aureus, the hydrogel was applied to the wound to further verify the killing effect on bacteria and wound healing effect of the hydrogel material in vivo. The Au@HNTs-chitin composite hydrogel exhibits high antibacterial and hemostatic activity as well as promoting wound healing function with low cytotoxicity. This study is significant for the development of high-performance wound dressings based on two commonly used biocompatible materials, which shows promising application in wound sterilization and healing.

9.
Bioact Mater ; 20: 404-417, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784636

RESUMO

Human cancers typically express a high level of tumor-promoting mutant p53 protein (Mutp53) with a minimal level of tumor-suppressing wild-type p53 protein (WTp53). In this regard, inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy. Herein, a new carrier-free nanoprodrug (i.e., Mn-ZnO2 nanoparticles) was developed for concurrent delivery of dual Zn-Mn ions and reactive oxygen species (ROS) within tumor to regulate the p53 protein for high anti-tumor efficacy. In response to the mild tumor acidic environment, the released Zn2+ and H2O2 from Mn-ZnO2 NPs induced ubiquitination-mediated proteasomal degradation of Mutp53, while the liberative Mn2+ and increased ROS level activated the ATM-p53-Bax pathway to elevate WTp53 level. Both in vitro and in vivo results demonstrated that pH-responsive decomposition of Mn-ZnO2 NPs could effectively elevate the intracellular dual Zn-Mn ions and ROS level and subsequently generate the cytotoxic hydroxyl radical (•OH) through the Fenton-like reaction. With the integration of multiple functions (i.e., carrier-free ion and ROS delivery, tumor accumulation, p53 protein modulation, toxic •OH generation, and pH-activated MRI contrast) in a single nanosystem, Mn-ZnO2 NPs demonstrate its superiority as a promising nanotherapeutics for p53-mutated tumor therapy.

10.
Bioact Mater ; 20: 418-433, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784637

RESUMO

Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque. It remains challenges for current practice to specifically identify, intervene and interrupt the development of caries while restoring defects. In this study, inspired by natural dental plaque, a stimuli-responsive multidrug delivery system (PMs@NaF-SAP) has been developed to prevent tooth decay and promote enamel restoration. Classic spherical core-shell structures of micelles dual-loaded with antibacterial and restorative agents are self-assembled into bacteria-responsive multidrug delivery system based on the pH-cleavable boronate ester bond, followed by conjugation with salivary-acquired peptide (SAP) to endow the nanoparticle with strong adhesion to tooth enamel. The constructed PMs@NaF-SAP specifically adheres to tooth, identifies cariogenic conditions and intelligently releases drugs at acidic pH, thereby providing antibacterial adhesion and cariogenic biofilm resistance, and restoring the microarchitecture and mechanical properties of demineralized teeth. Topical treatment with PMs@NaF-SAP effectively diminishes the onset and severity of caries without impacting oral microbiota diversity or surrounding mucosal tissues. These findings demonstrate this novel nanotherapy has potential as a promising biomedical application for caries prevention and tooth defect restoration while resisting biofilm-associated diseases in a controlled manner activated by pathological bacteria.

11.
Bioact Mater ; 20: 368-380, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784638

RESUMO

Recently, a number of studies reported that casein was composed of various multifunctional bioactive peptides such as casein phosphopeptide and ß-casochemotide-1 that bind calcium ions and induce macrophage chemotaxis, which is crucial for bone homeostasis and bone fracture repair by cytokines secreted in the process. We hypothesized that the effects of the multifunctional biopeptides in casein would contribute to improving bone regeneration. Thus, we designed a tissue engineering platform that consisted of casein and polyvinyl alcohol, which was a physical-crosslinked scaffold (milk-derived protein; MDP), via simple freeze-thaw cycles and performed surface modification using 3,4-dihydroxy-l-phenylalanine (DOPA), a mussel adhesive protein, for immobilizing adhesive proteins and cytokines for recruiting cells in vivo (MDP-DOPA). Both the MDP and MDP-DOPA groups proved indirectly contribution of macrophages migration as RAW 264.7 cells were highly migrated toward materials by contained bioactive peptides. We implanted MDP and MDP-DOPA in a mouse calvarial defect orthotopic model and evaluated whether MDP-DOPA showed much faster mineral deposition and higher bone density than that of the no-treatment and MDP groups. The MDP-DOPA group showed the accumulation of host M2 macrophages and mesenchymal stem cells (MSCs) around the scaffold, whereas MDP presented mostly M1 macrophages in the early stage.

12.
Bioact Mater ; 20: 339-354, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784639

RESUMO

Myocardial infarction (MI) leads to massive cardiomyocyte death and deposition of collagen fibers. This fibrous tissue disrupts electrical signaling in the myocardium, leading to cardiac systolic and diastolic dysfunction, as well as arrhythmias. Conductive hydrogels are a promising therapeutic strategy for MI. Here, we prepared a highly water-soluble conductive material (GP) by grafting polypyrrole (PPy) onto non-conductive gelatin. This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum (OXG) and gelatin to construct an injectable conductive hydrogel. The prepared self-healing OGGP3 (3 wt% GP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the natural heart. The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI. We found that the cardiac function of the rats treated with OGGP3 was improved, making it more difficult to induce arrhythmias. The electrical resistivity of myocardial fibrous tissue was reduced, and the conduction velocity of myocardial tissue was increased. Histological analysis showed reduced infarct size, increased left ventricular wall thickness, increased vessel density, and decreased inflammatory response in the infarcted area. Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation, thus showing its potential for the treatment of MI.

13.
Bioact Mater ; 20: 381-403, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35784640

RESUMO

Rigidity (or stiffness) of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors, such as contractility, motility, and spreading, and the resultant pathophysiological phenomena. Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events, including migration, lineage specification, and mechanical memory. Moreover, the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control, tissue repair, and disease progression. Thus, here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors, with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems, further discussion of the events and considerations in tissue-mimicking 3D conditions, and then examination of the in vivo findings that concern material/matrix rigidity. The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.

14.
Neural Regen Res ; 18(1): 18-22, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799503

RESUMO

Alzheimer's disease is a progressive and fatal neurodegenerative disorder that starts many years before the onset of cognitive symptoms. Identifying novel biomarkers for Alzheimer's disease has the potential for patient risk stratification, early diagnosis, and disease monitoring in response to therapy. A novel class of biomarkers is extracellular vesicles given their sensitivity and specificity to specific diseases. In addition, extracellular vesicles can be used as novel biological therapeutics given their ability to efficiently and functionally deliver therapeutic cargo. This is critical given the huge unmet need for novel treatment strategies for Alzheimer's disease. This review summarizes and discusses the most recent findings in this field.

15.
Neural Regen Res ; 18(1): 5-17, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799502

RESUMO

Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical, mechanical, noxious and other stimuli. Prostaglandin D2, prostaglandin E2, prostaglandin F2α, prostaglandin I2 and thromboxane-A2 interact with five major receptors (and their sub-types) to elicit specific downstream cellular and tissue actions. In general, prostaglandins have been associated with pain, inflammation, and edema when they are present at high local concentrations and involved on a chronic basis. However, in acute settings, certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation, providing cellular protection, regulating sleep, and enhancing blood flow, to lowering intraocular pressure to prevent the development of glaucoma, a blinding disease. Several classes of prostaglandins are implicated (or are considered beneficial) in certain central nervous system dysfunctions (e.g., Alzheimer's, Parkinson's, and Huntington's diseases; amyotrophic lateral sclerosis and multiple sclerosis; stroke, traumatic brain injuries and pain) and in ocular disorders (e.g., ocular hypertension and glaucoma; allergy and inflammation; edematous retinal disorders). This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease, and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists, polyunsaturated fatty acids, and cyclooxygenase inhibitors.

16.
Neural Regen Res ; 18(1): 23-30, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799504

RESUMO

Injuries to the spinal cord result in permanent disabilities that limit daily life activities. The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic injuries. Despite decades of research, there is still no efficient treatment for spinal cord injury. Many strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord injury. Among these, molecular compounds are currently being used for neurological recovery, with promising results. These molecules target the axon collapsed growth cone, the inhibitory microenvironment, the survival of neurons and glial cells, and the re-establishment of lost connections. In this review we focused on molecules that are being used, either in preclinical or clinical studies, to treat spinal cord injuries, such as drugs, growth and neurotrophic factors, enzymes, and purines. The mechanisms of action of these molecules are discussed, considering traumatic spinal cord injury in rodents and humans.

17.
Neural Regen Res ; 18(1): 31-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799505

RESUMO

Stroke is the second leading cause of death and a major cause of disability worldwide, and biological sex is an important determining factor in stroke incidence and pathology. From childhood through adulthood, men have a higher incidence of stroke compared with women. Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke. Autophagy is a self-degrading cellular process orchestrated by multiple core proteins, which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy vesicles fuse with lysosomes or endosomes. The levels and the activity of components of these signaling pathways and of autophagy-related proteins can be altered during ischemic insults. Ischemic stroke activates autophagy, however, whether inhibiting autophagy after stroke is beneficial in the brain is still under a debate. Autophagy is a potential mechanism that may contribute to differences in stroke progression between the sexes. Furthermore, the effects of manipulating autophagy may also differ between the sexes. Mechanisms that regulate autophagy in a sex-dependent manner in ischemic stroke remain unexplored. In this review, we summarize clinical and pre-clinical evidence for sex differences in stroke. We briefly introduce the autophagy process and summarize the effects of gonadal hormones in autophagy in the brain and discuss X-linked genes that could potentially regulate brain autophagy. Finally, we review pre-clinical studies that address the mechanisms that could mediate sex differences in brain autophagy after stroke.

18.
Neural Regen Res ; 18(1): 38-46, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799506

RESUMO

Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.

19.
Neural Regen Res ; 18(1): 47-50, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799507

RESUMO

Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral palsy. Extensive clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain growth. Multiple pathways are involved in the pathogenesis of perinatal inflammation. However, studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine interleukin-1. In this review, we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain injury. We also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage, and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist, anakinra, as a safe and effective therapeutic intervention. We reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment, and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

20.
Neural Regen Res ; 18(1): 51-56, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799508

RESUMO

Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes. During this physiological process, the brain is the most affected organ due to changes in its structural and chemical functions, such as changes in plasticity and decrease in the number, diameter, length, and branching of dendrites and dendritic spines. Likewise, it presents a great reduction in volume resulting from the contraction of the gray matter. Consequently, aging can affect not only cognitive functions, including learning and memory, but also the quality of life of older people. As a result of the phenomena, various molecules with notable neuroprotective capacity have been proposed, which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases. It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models. This review aims to describe the neurotrophic potential of molecules such as resveratrol (3,5,4'-trihydroxystilbene), neurotrophins (brain-derived neurotrophic factor), and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin, cerebrolysin, neuropeptide-12, and rapamycin. Most of these molecules have been evaluated by our research group. Studies suggest that these molecules exert an important therapeutic potential, restoring brain function in aging conditions or models of neurodegenerative diseases. Hence, our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.

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