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1.
Transplant Cell Ther ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38663767

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy against a variety of malignant and nonmalignant disorders. However, acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) commonly complicate this approach, culminating in substantial morbidities and mortalities. The integumentary system is the preponderant organ involved in cGVHD, and its response to existing treatments, including well-versed immunosuppressants and novel targeted therapies, is not desirable. Despite the rarity, ulcers of sclerotic skin cGVHD are treatment-refractory and associated with significant morbidities and an exaggerated risk of infectious complications. Platelet-rich plasma (PRP) and its derivatives are endowed with growth factors and proangiogenic molecules and hold regenerative potential. OBJECTIVES: To assess the safety and efficacy of the application of platelet gel-containing dressing for the management of ulcerative skin cGVHD in pediatric patients. STUDY DESIGN: This randomized trial is conducted at the hematopoietic stem cell transplantation unit of the Children's Medical Center Hospital in Tehran, Iran. Twenty-one pediatric patients (aged between 5 and 15 years) were initially enrolled, and 16 met the inclusion criteria. All cases (four females) were recipients of allo-HSCT who had been complicated with symmetrically or near-symmetrically ulcerative sclerotic skin cGVHD. Fresh umbilical cord blood (UCB) was obtained from healthy donors and underwent centrifugation using a novel PRP preparation kit in a single-step process. Platelet gel was produced by adding thrombin to the isolated buffy coat layer. Two similar ulcers of each patient were randomized to receive either conventional dressing or platelet gels up to 6 times. At each time point evaluation, ulcer size and its relative reduction compared to the basal size were recorded. RESULTS: Included patients received a total of 80 platelet gel-containing dressings. While the mean sizes of randomized ulcers at the beginning of the study were similar, their differences became significant 15 days after the initiation of intervention (P = 0.019). In addition, the mean reduction in the ulcers' surface area (in comparison to their baseline values) was significantly higher for the intervention arm at all evaluation points (P = 0.001 for day five and P < 0.001 for subsequent time points). At the end of the trial, the number of ulcers with a more than 50% reduction in size was 14 (87.5%) in the intervention arm (including six completely healed ulcers) versus one (6.25%, which was not completely healed) in the control arm (P < 0.001). None of the patients exhibited any localized or systemic treatment-related adverse events. CONCLUSIONS: In this study, using a relatively large number of cases, we showed that UCB-derived platelet gel is a safe, feasible, and effective curative approach for skin ulcers of sclerotic skin cGVHD in pediatric patients. Designing upcoming trials on the efficacy of this therapeutic approach for ocular, mucosal, and acute skin GVHD is prudent. TRIAL REGISTRATION: Retrospectively registered at the Iranian Registry of Clinical Trials (registration number IRCT20190101042197N1) on August 24, 2020.

2.
J Diabetes ; 16(5): e13554, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38664883

RESUMO

Diabetic wounds cannot undergo normal wound healing due to changes in the concentration of hyperglycemia in the body and soon evolve into chronic wounds causing amputation or even death of patients. Diabetic wounds directly affect the quality of patients and social medical management; thus researchers started to focus on skin transplantation technology. The acellular fish skin grafts (AFSGs) are derived from wild fish, which avoids the influence of human immune function and the spread of the virus through low-cost decellularization. AFSGs contain a large amount of collagen and omega-3 polyunsaturated fatty acids and they have an amazing effect on wound regeneration. However, after our search in major databases, we found that there were few research trials in this field, and only one was clinically approved. Therefore, we summarized the advantages of AFSGs and listed the problems faced in clinical use. The purpose of this paper is to enable researchers to better carry out original experiments at various stages.


Assuntos
Transplante de Pele , Cicatrização , Humanos , Animais , Transplante de Pele/métodos , Peixes , Pé Diabético/cirurgia , Pé Diabético/terapia
3.
Chem Asian J ; : e202400187, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38665128

RESUMO

The wounds, arises from accidents, burns, surgeries, diabetes, and trauma, can significantly impact well-being and present persistent clinical challenges. Ideal wound dressings should be flexible, stable, antibacterial, antioxidant and anti-inflammatory in nature, facilitating a scarless rapid wound healing. Initiatives were taken to create antibacterial cotton fabrics by incorporating agents like antibiotics and metallic nanoparticles. However, due to a lack of multifunctionality, these materials were not highly effective in causing scarless and rapid wound healing. In this article, nickel thiocyanate nanoparticle (NiSCN-NPs) impregnated cotton gauze wound dressing (NiSCN-CG) was developed. These nanoparticles were non-toxic to normal human cell lines till 1 mg/mL dose and did not cause skin irritation in the rat model. Further, NiSCN-NPs exhibited antimicrobial, antibiofilm and antioxidant activities confirmed using different in vitro experiments. In vivo wound healing studies in rat models using NiSCN-CG demonstrated rapid scarless wound healing. The nickel thiocyanate impregnated cotton gauze presents a novel approach in scarless wound healing, and as an antimicrobial agent, offering a promising solution for diverse wounds and infections in the future.

4.
J Clin Orthop Trauma ; 51: 102385, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665678

RESUMO

Aim: This study aimed to compare the effectiveness of a customized vacuum-assisted dressing to traditional betadine dressings for wounds in open fractures. Materials and methods: In this prospective comparative study, 30 patients from two groups-group A receiving V.A.C. while group B receiving traditional dressing-were given data from sixty participants with open fractures. Wound was evaluated on days 0, 3, 7, 11, and 15 of the study. Results: In group A, there was a statistically significant decrease in the mean dimension of the wound overall (15.66 mm vs. 7.4 mm in group B), and it took an average of 9.83 days for healthy granulation tissue to emerge. In contrast to the 21 patients who had split skin grafting, five patients needed a flap as a final closure surgery. In group B, it took an average of 17 days for healthy granulation tissue to emerge. The authors used split skin grafting to close the wounds in 18 patients, and the wound was allowed to heal by secondary intention in 8 patients, while the flap was used in 4 patients. Conclusion: On comparing the modified Vacuum-assisted dressing to the standard dressing, there was considerable wound contraction and accelerated healing. Therefore, the authors observed that vacuum-assisted dressing treatment is superior to traditional betadine dressing in open fractures.

5.
Int J Pharm ; 657: 124138, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642619

RESUMO

In clinical practice, wound care has always been challenging. Hydrogels play a key role in facilitating active wound recovery by absorbing exudates, maintaining moisture, and alleviating pain through cooling. In this study, type I collagen was isolated from the skin of crucian carp (Carassius carassius) and verified by amino acid analysis, FTIR, and SDS-PAGE. By adopting a new approach, luteolin was added to collagen hydrogels in situ after being dissolved in an alkaline solution. XRD and SEM confirmed the luteolin was incorporated and entirely distributed throughout the hydrogel. The plastic compression improved the young's modulus of hydrogel to 15.24 ± 0.59 kPa, which is adequate for wound protection. The drug loading efficiency was 98 ± 1.47 % in the selected formulation. The luteolin-incorporated hydrogel enabled regulated drug release. We assessed the cytotoxicity using MTT and live-dead assays, as well as examined the hemocompatibility to determine the biocompatibility of the hydrogel. In vivo experiments showed that the hydrogel with luteolin had the highest wound closure rate (94.01 ± 2.1 %) and improved wound healing with granular tissue formation, collagen deposition, and re-epithelialization. These findings indicate that this efficient drug delivery technology can accelerate the process of wound healing.

6.
Mil Med Res ; 11(1): 23, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637905

RESUMO

Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.


Assuntos
Diabetes Mellitus , Cicatrização , Humanos , Cicatrização/fisiologia , Desbridamento/métodos , Pele , Imunoterapia
7.
Acta Biomater ; 179: 61-82, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38579919

RESUMO

In the field of tissue engineering, local hypoxia in large-cell structures (larger than 1 mm3) poses a significant challenge. Oxygen-releasing biomaterials supply an innovative solution through oxygen ⁠ delivery in a sustained and controlled manner. Compared to traditional methods such as emulsion, sonication, and agitation, microfluidic technology offers distinct benefits for oxygen-releasing material production, including controllability, flexibility, and applicability. It holds enormous potential in the production of smart oxygen-releasing materials. This review comprehensively covers the fabrication and application of microfluidic-enabled oxygen-releasing biomaterials. To begin with, the physical mechanism of various microfluidic technologies and their differences in oxygen carrier preparation are explained. Then, the distinctions among diverse oxygen-releasing components in regards for oxygen-releasing mechanism, oxygen-carrying capacity, and duration of oxygen release are presented. Finally, the present obstacles and anticipated development trends are examined together with the application outcomes of oxygen-releasing biomaterials based on microfluidic technology in the biomedical area. STATEMENT OF SIGNIFICANCE: Oxygen is essential for sustaining life, and hypoxia (a condition of low oxygen) is a significant challenge in various diseases. Microfluidic-based oxygen-releasing biomaterials offer precise control and outstanding performance, providing unique advantages over traditional approaches for tissue engineering. However, comprehensive reviews on this topic are currently lacking. In this review, we provide a comprehensive analysis of various microfluidic technologies and their applications for developing oxygen-releasing biomaterials. We compare the characteristics of organic and inorganic oxygen-releasing biomaterials and highlight the latest advancements in microfluidic-enabled oxygen-releasing biomaterials for tissue engineering, wound healing, and drug delivery. This review may hold the potential to make a significant contribution to the field, with a profound impact on the scientific community.


Assuntos
Materiais Biocompatíveis , Oxigênio , Engenharia Tecidual , Oxigênio/química , Humanos , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Animais , Microfluídica/métodos
8.
Mater Today Bio ; 26: 101056, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38660474

RESUMO

Diabetic foot ulcer (DFU) is a highly morbid complication in patients with diabetes mellitus, necessitating the development of innovative pharmaceuticals to address unmet medical needs. Sodium ion (Na+) is a well-established mediator for membrane potential and osmotic equilibrium. Recently, Na+ transporters have been identified as a functional regulator of regeneration. However, the role of Na+ in the intricate healing process of mammalian wounds remains elusive. Here, we found that the skin wounds in hyponatremic mice display a hard-to-heal phenotype. Na+ ionophores that were employed to increase intracellular Na+ content could facilitate keratinocyte proliferation and migration, and promote angiogenesis, exhibiting diverse biological activities. Among of them, monensin A emerges as a promising agent for accelerating the healing dynamics of skin wounds in diabetes. Mechanistically, the elevated mitochondrial Na+ decelerates inner mitochondrial membrane fluidity, instigating the production of reactive oxygen species (ROS), which is identified as a critical effector on the monensin A-induced improvement of wound healing. Concurrently, Na+ ionophores replenish H+ to the mitochondrial matrix, causing an enhancement of mitochondrial energy metabolism to support productive wound healing programs. Our study unfolds a new role of Na+, which is a pivotal determinant in wound healing. Furthermore, it directs a roadmap for developing Na+ ionophores as innovative pharmaceuticals for treating chronic dermal wounds in diabetic patients.

9.
Photobiomodul Photomed Laser Surg ; 42(4): 285-293, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38662503

RESUMO

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Modelos Animais de Doenças , Terapia com Luz de Baixa Intensidade , Ratos Sprague-Dawley , Extração Dentária , Cicatrização , Ácido Zoledrônico , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Ratos , Ácido Zoledrônico/farmacologia , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Conservadores da Densidade Óssea , Difosfonatos/farmacologia , Lasers Semicondutores/uso terapêutico , Imidazóis/farmacologia , Masculino
10.
Sci Rep ; 14(1): 9103, 2024 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643292

RESUMO

Quantitative assessment of cell migration in vitro is often required in fundamental and applied research from different biomedical areas including wound repair, tumor metastasis or developmental biology. A collection of assays has been established throughout the years like the most widely used scratch assay or the so-called barrier assay. It is the principle of these assays to introduce a lesion into an otherwise confluent monolayer in order to study the migration of cells from the periphery into this artificial wound and determine the migration rate from the time necessary for wound closure. A novel assay makes use of photosensitizers doped into a polystyrene matrix. A thin layer of this composite material is coated on the bottom of regular cell culture ware showing perfect biocompatibility. When adherent cells are grown on this coating, resonant excitation of the photosensitizer induces a very local generation of 1O2, which kills the cells residing at the site of illumination. Cells outside the site of illumination are not harmed. When excitation of the photosensitizer is conducted by microscopic illumination, high-precision wounding in any size and geometry is available even in microfluidic channels. Besides proof-of-concept experiments, this study gives further insight into the mechanism of photosensitizer-mediated cell wounding.


Assuntos
Fármacos Fotossensibilizantes , Cicatrização , Fármacos Fotossensibilizantes/farmacologia , Técnicas de Cultura de Células , Microfluídica , Movimento Celular
11.
Regen Ther ; 27: 342-353, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38645281

RESUMO

Background: One of the key obstacles to the healing of diabetic wound is the persistence of active inflammation. We previously demonstrated the potential of cell-free fat extract (CEFFE) to promote the healing of diabetic wounds, and annexin A5 (A5) is a crucial anti-inflammatory protein within CEFFE. This study aimed to evaluate the therapeutic potential of A5 in diabetic wounds. Methods: A5 was loaded into GelMA hydrogels and applied to skin wounds of diabetic mice in vivo. The diabetic wounds with the treatment of GelMA-A5 were observed for 14 days and evaluated by histological analysis. Accessment of inflammation regulation were conducted through anti-CD68 staining, anti-CD86 and anti-CD206 staining, and qRT-PCR of wound tissue. In presence of A5, macrophages stimulated by lipopolysaccharide (LPS) in vitro, and detected through qRT-PCR, flow cytometry, and immunocytofluorescence staining. Besides, epithelial cells were co-cultured with A5 for epithelialization regulation by CCK-8 assay and cell migration assay. Results: A5 could promote diabetic wound healing and regulate inflammations by promoting the transition of macrophages from M1 to M2 phenotype. In vitro experiments demonstrated that A5 exerted a significant effect on reducing pro-inflammatory factors and inhibiting the polarization of macrophages from M0 toward M1 phenotype. A5 significantly promoted the migration of epithelial cells. Conclusion: Annexin A5 has a significant impact on the regulation of macrophage inflammation and promotion of epithelialization.

12.
Biomed Eng Lett ; 14(3): 537-548, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38645584

RESUMO

Wound healing is a complex biological process crucial for restoring tissue integrity and preventing infections. The development of advanced materials that facilitate and expedite the wound-healing process has been a focal point in biomedical research. In this study, we aimed to enhance the wound-healing potential of hydrogel scaffolds by incorporating graphene oxide and poly (ethylene glycol) methyl ether methacrylate (MEO2MA). Various masses of graphene oxide were added to MEO2MA hydrogels via free radical polymerisation. Comprehensive characterizations, encompassing mechanical properties, and biocompatibility assays, were conducted to evaluate the hydrogels' suitability for wound healing. In vitro experiments demonstrated that the graphene oxide-based hydrogels exhibited a proper swelling degree and tensile strength, responding effectively to moisture conditions and adhesiveness for wound healing. Notably, the tensile strength significantly increased to 626 kPa in the graphene oxide hydrogels. Biocompatibility assessments revealed that the graphene oxide/MEO2MA hydrogels were non-toxic to human dermal fibroblast cell growth, with no significant difference in cell viability observed in the graphene oxide/MEO2MA hydrogel (H-HG) group. In a rat skin experiment, the wound-healing rate of the hydrogel incorporating graphene oxide surpassed that of the pristine hydrogel after a 15-day treatment, achieving over 95% wound closure in the H-HG group. The histopathological analysis further supported the efficacy of the H-HG hydrogel dressing in promoting more effective tissue regeneration. These results collectively highlight the potential of the graphene oxide/MEO2MA hydrogel scaffold as a promising dressing for medical applications.

13.
Biomed Eng Lett ; 14(3): 605-616, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38645591

RESUMO

Wound healing involves a complex and dynamic interplay among various cell types, cytokines, and growth factors. Macrophages and transforming growth factor-ß1 (TGF-ß1) play an essential role in different phases of wound healing. Cold atmospheric plasma has a wide range of applications in the treatment of chronic wounds. Hence, we aimed to investigate the safety and efficacy of a custom-made plasma device in a full-thickness skin defect mouse model. Here, we investigated the wound tissue on days 6 and 12 using histology, qPCR, and western blotting. During the inflammation phase of wound repair, macrophages play an important role in the onset and resolution of inflammation, showing decreased F4/80 on day 6 of plasma treatment and increased TGF-ß1 levels. The plasma-treated group showed better epidermal epithelialization, dermal fibrosis, collagen maturation, and reduced inflammation than the control group. Our findings revealed that floating electrode-dielectric barrier discharge (FE-DBD)-based atmospheric-pressure plasma promoted significantly faster wound healing in the plasma-treated group than that in the control group with untreated wounds. Hence, plasma treatment accelerated wound healing processes without noticeable side effects and suppressed pro-inflammatory genes, suggesting that FE-DBD-based plasma could be a potential therapeutic option for treating various wounds.

14.
Front Bioeng Biotechnol ; 12: 1386896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646012

RESUMO

Introduction: Autologous cell suspension (ACS)-based therapy represents a highly promising approach for burns and chronic wounds. However, existing technologies have not achieved the desired clinical success due to several limitations. To overcome practical and cost-associated obstacles of existing ACS methods, we have established a novel methodology for rapid, enzymatic disaggregation of human skin cells and their isolation using a procedure that requires no specialist laboratory instrumentation and is performed at room temperature. Methods: Cells were isolated using enzymatic disaggregation of split-thickness human skin followed by several filtration steps for isolation of cell populations, and cell viability was determined. Individual population recovery was confirmed in appropriate culture medium types, and the presence of epidermal stem cells (EpSCs) within keratinocyte sub-populations was defined by flow cytometry via detection of CD49 and CD71. Positive mediators of wound healing secreted by ACS-derived cultures established on a collagen-based wound-bed mimic were detected by proteome arrays and quantified by ELISA, and the role of such mediators was determined by cell proliferation assays. The effect of ACS-derived conditioned-medium on myofibroblasts was investigated using an in-vitro model of myofibroblast differentiation via detection of α-SMA using immunoblotting and immunofluorescence microscopy. Results: Our methodology permitted efficient recovery of keratinocytes, fibroblasts and melanocytes, which remained viable upon long-term culture. ACS-derivatives comprised sub-populations with the CD49-high/CD71-low expression profile known to demarcate EpSCs. Via secretion of mitogenic factors and wound healing-enhancing mediators, the ACS secretome accelerated keratinocyte proliferation and markedly curtailed cytodifferentiation of myofibroblasts, the latter being key mediators of fibrosis and scarring. Discussion: The systematic characterisation of the cell types within our ACS isolates provided evidence for their superior cell viability and the presence of EpSCs that are critical drivers of wound healing. We defined the biological properties of ACS-derived keratinocytes, which include ability to secrete positive mediators of wound healing as well as suppression of myofibroblast cytodifferentiation. Thus, our study provides several lines of evidence that the established ACS isolates comprise highly-viable cell populations which can physically support wound healing and possess biological properties that have the potential to enhance not only the speed but also the quality of wound healing.

15.
Cureus ; 16(3): e56726, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646389

RESUMO

Introduction Negative-pressure wound therapy (NPWT) has been used for decades as an established treatment modality for complex wounds, now commonplace in hospitals and various clinical and outpatient settings. Several studies have noted improved healing outcomes with this device, but the current state of literature is in debate on both clinical and economic effectiveness. The use of NPWT can become expensive, largely because of the complexity of wounds and the need for outpatient management, from which a majority of the benefit is derived. This creates a disparity in access to this therapy. A lack of insurance and limited access to healthcare that is present in minority populations contribute to this inequality. Methods We reviewed the clinical courses of eight patients who were treated with NPWT at a single acute care facility in an underserved area caring for a minority population. Results We describe several different anatomic wounds along with details including the size of wounds, number of debridements, length of hospital stay, duration of treatment, and ensuing courses of the minority patients who received NPWT for the entire duration of their wound care course. Conclusions This case series demonstrates desirable wound healing outcomes with the use of NPWT in the minority population. The authors draw attention to the outpatient benefit of this device that may be lost in those with limited insurance in minority populations and seek to encourage further studies in this population in resource-limited settings to determine its true clinical effectiveness.

16.
Front Immunol ; 15: 1371743, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646541

RESUMO

Granzymes are a family of serine proteases, composed of five human members: GA, B, H, M and K. They were first discovered in the 1980s within cytotoxic granules released during NK cell- and T cell-mediated killing. Through their various proteolytic activities, granzymes can trigger different pathways within cells, all of which ultimately lead to the same result, cell death. Over the years, the initial consideration of granzymes as mere cytotoxic mediators has changed due to surprising findings demonstrating their expression in cells other than immune effectors as well as new intracellular and extracellular activities. Additional roles have been identified in the extracellular milieu, following granzyme escape from the immunological synapse or their release by specific cell types. Outside the cell, granzyme activities mediate extracellular matrix alteration via the degradation of matrix proteins or surface receptors. In certain contexts, these processes are essential for tissue homeostasis; in others, excessive matrix degradation and extensive cell death contribute to the onset of chronic diseases, inflammation, and autoimmunity. Here, we provide an overview of both the physiological and pathological roles of granzymes, highlighting their utility while also recognizing how their unregulated presence can trigger the development and/or worsening of diseases.


Assuntos
Granzimas , Humanos , Granzimas/metabolismo , Animais , Matriz Extracelular/metabolismo , Matriz Extracelular/imunologia , Inflamação/imunologia , Células Matadoras Naturais/imunologia
17.
Protein Sci ; 33(5): e4993, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38647395

RESUMO

Optogenetic tools (OTs) operating in the far-red and near-infrared (NIR) region offer advantages for light-controlling biological processes in deep tissues and spectral multiplexing with fluorescent probes and OTs acting in the visible range. However, many NIR OTs suffer from background activation in darkness. Through shortening linkers, we engineered a novel NIR OT, iLight2, which exhibits a significantly reduced background activity in darkness, thereby increasing the light-to-dark activation contrast. The resultant optimal configuration of iLight2 components suggests a molecular mechanism of iLight2 action. Using a biliverdin reductase knock-out mouse model, we show that iLight2 exhibits advanced performance in mouse primary cells and deep tissues in vivo. Efficient light-controlled cell migration in wound healing cellular model demonstrates the possibility of using iLight2 in therapy and, overall, positions it as a valuable addition to the NIR OT toolkit for gene transcription applications.

18.
Health Sci Rep ; 7(4): e2036, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650719

RESUMO

Background: Diabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy. Methodology: A comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English-language literature that explored the relationship between DFU, MSCs, and related factors. Results and Discussion: Numerous studies are being conducted and have demonstrated that MSCs can induce re-epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits. Conclusion: The incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.

19.
J Biomed Opt ; 29(4): 046003, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650893

RESUMO

Significance: Current methods for wound healing assessment rely on visual inspection, which gives qualitative information. Optical methods allow for quantitative non-invasive measurements of optical properties relevant to wound healing. Aim: Spatial frequency domain imaging (SFDI) measures the absorption and reduced scattering coefficients of tissue. Typically, SFDI assumes homogeneous tissue; however, layered structures are present in skin. We evaluate a multi-frequency approach to process SFDI data that estimates depth-specific scattering over differing penetration depths. Approach: Multi-layer phantoms were manufactured to mimic wound healing scattering contrast in depth. An SFDI device imaged these phantoms and data were processed according to our multi-frequency approach. The depth sensitive data were then compared with a two-layer scattering model based on light fluence. Results: The measured scattering from the phantoms changed with spatial frequency as our two-layer model predicted. The performance of two δ-P1 models solutions for SFDI was consistently better than the standard diffusion approximation. Conclusions: We presented an approach to process SFDI data that returns depth-resolved scattering contrast. This method allows for the implementation of layered optical models that more accurately represent physiologic parameters in thin tissue structures as in wound healing.

20.
Int Wound J ; 21(4): e14886, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651532

RESUMO

Negative pressure injury is one of the auxiliary methods of treating diabetes foot ulcers. It has been shown to be superior to conventional techniques in randomized controlled trials (RCTs). Nevertheless, the results of observational research are still scarce. A systematic review of RCTs and observations was carried out to evaluate the effectiveness and security of negative pressure wound therapy (NPWT) treatment for diabetes foot ulcers. Three English e-databases have been found for NPWT research. The meta-analyses of the comparative studies provided point estimates of results. Intermediate results were given as median and binary values were given in the form of odds ratios (OR). Seventeen trials, 13 RCTs and four randomized, controlled trials were found in the survey. Of these, 831 were treated with NPWT, 834 were treated with standard therapy. A total of 14 studies have been conducted to investigate the influence of NPWT on the healing of diabetic foot ulcers(DFU). In the study, NPWT was shown to speed up the healing of the wound in DFU patients(OR, 2.57; 95% CI, 1.72, 3.85 p < 0.0001). A subgroup analysis showed that NPWT was associated with an acceleration of the wound healing rate in 10 RCT trials (OR, 2.48; 95% CI, 1.58, 3.89 p < 0.001). In the four nRCT trials, NPWT was also shown to speed up the healing of the wound(OR, 2.95; 95% CI, 1.03, 8.42 p = 0.04). In 11 studies, the influence of NPWT on amputations of diabetes mellitus (DM) foot ulcers was investigated. The results showed that NPWT was associated with a reduction in amputations (OR, 0.53; 95% CI, 0.37, 0.74 p = 0.0002).In a subgroup of RCT trials, nine RCT trials showed a reduction in amputations(OR, 0.61; 95% CI, 0.43, 0.87 p = 0.007). In both nRCT trials, NPWT also showed a reduction in amputations (OR, 0.03; 95% CI, 0.00, 0.24 p = 0.001). Generally speaking, NPWT can help to heal the wound and lower the risk of amputations in people with diabetes. The subgroup analysis showed similar results for the RCT and non-RCT trials. NPWT can be used to treat diabetes foot ulcers caused by diabetes.

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