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1.
Mol Cancer ; 23(1): 214, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39343883

RESUMEN

Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.


Asunto(s)
Neoplasias , ARN Circular , ARN Largo no Codificante , Humanos , ARN Circular/genética , ARN Largo no Codificante/genética , Neoplasias/genética , Animales , Péptidos/genética , Biomarcadores de Tumor/genética , Sistemas de Lectura Abierta , Regulación Neoplásica de la Expresión Génica , Susceptibilidad a Enfermedades
2.
J Foot Ankle Surg ; 63(4): 435-442, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38438102

RESUMEN

In recent years, anterior tibiofibular ligament-distal fascicle transfers for anterior talofibular ligament augmentation repair have proposed. However, a comprehensive biomechanical study on the anterior tibiofibular ligament-distal fascicle transfer is still lacking. We are established four distinct groups, namely the normal, the anterior talofibular ligament rupture, the anterior talofibular ligament repair, and the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer. We assessed the anterior drawer test and varus stress test of the ankle in each group. Moreover, we employed the model to simulate and compute the total displacement and von-Mises stress of the talus cartilage at varying gait phases, including foot strike, tibia vertical, and toe-off phases. The results of the anterior drawer test and varus stress test revealed that the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group exhibited greater closeness to the normal group. Regarding von-Mises stress in cartilage, the three gait instants had higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Nevertheless, regarding total displacement, the toe-off phases exhibited higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Using ATiFL-DF transfer to augment ATFL repair is a potential feasible procedure. However, this procedure could potentially compromise the anterior tibiofibular ligament's contribution to the dynamic stability of the ankle. Therefore, we recommend conducting further in-depth research to ensure the suitability and success of this technique in a clinical environment.


Asunto(s)
Articulación del Tobillo , Análisis de Elementos Finitos , Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Humanos , Ligamentos Laterales del Tobillo/cirugía , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/fisiopatología , Articulación del Tobillo/cirugía , Articulación del Tobillo/fisiopatología , Fenómenos Biomecánicos , Adulto , Masculino , Enfermedad Crónica
3.
Foot Ankle Surg ; 30(1): 74-78, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37748980

RESUMEN

BACKGROUND: Osseous structures have been demonstrated as risk factors for chronic ankle instability (CAI). Previously, the researchers only focused on the osseous structures of ankle, but ignored the osseous structures of subtalar joint(STJ). Accordingly, the aim of our study was to investigate the morphological characteristics of STJ osseous structures in CAI. METHODS: 52 patients with CAI and 52 sex- and age- matched control subjects were enrolled from The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. The lateral radiographs of ankle in weight-bearing were used to compare the diversity of the two groups. Specifically, The Length of calcaneus, Calcaneal facet height and Absolute foot height, Böhler's angle, Gissane's angle, Calcaneal inclination angle, Talocalcaneal angle, Tibiotalar angle, Tibiocalcaneal angle, Talar-horizontal angle, talar declination angle, facet inclination angle were gauged in the two groups. RESULTS: The Böhler's angle, Calcaneal inclination, Talocalcaneal angle, Tibiotalar angle, Talar-horizontal angle, Talar declination angle, Facet inclination angle and Absolute foot height of CAI group were significantly higher than normal control group (P < 0.05). There were no significant differences in Gissane's angle, Tibiocalcaneal angle, Length of calcaneus and Calcaneal facet height between patients with CAI and normal controls (P > 0.05). CONCLUSIONS: The osseous structures of STJ in CAI patients are different from normal people in morphology. Therefore, we should pay more attention to the changes of STJ anatomical parameters in the diagnosis and prevention of CAI. LEVEL OF EVIDENCE: Ⅲ.


Asunto(s)
Calcáneo , Inestabilidad de la Articulación , Articulación Talocalcánea , Humanos , Tobillo , Articulación Talocalcánea/diagnóstico por imagen , Pie , Calcáneo/cirugía , Radiografía , Articulación del Tobillo/diagnóstico por imagen , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/etiología
4.
Foot Ankle Surg ; 30(7): 582-586, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38760281

RESUMEN

BACKGROUND: The study was to establish a novel classification of the morphological characteristics of fibula anterior-inferior margin (FAIM), which was reported in few studies. METHODS: The 501 images with three-dimensional computed tomography (3D CT) reconstruction were reviewed retrospectively. The width, height, thickness, long axis, short axis, and lateral malleolus angle were measured. RESULTS: The FAIM was divided into Angular, Flat, and Arc. The Flat has no distinct fibular obscure tubercles (FOT). The short axis of Angular and Arc were more significant than the Flat (P < 0. 05). The height of left was larger than the right, but short axis was less than it (P < 0.05). The height and short axis of males were larger than the females (P < 0.05). CONCLUSIONS: A novel classification (the Angular, Flat and Arc) of FAIM was identified based on lateral malleolus morphology, and it suggested that not all have obvious FOT. LEVEL OF EVIDENCE: Level Ⅲ, retrospective study.


Asunto(s)
Peroné , Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Peroné/diagnóstico por imagen , Peroné/anatomía & histología , Anciano , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/anatomía & histología , Adulto Joven , Adolescente
5.
J Transl Med ; 21(1): 892, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38066566

RESUMEN

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Macrófagos , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismo , Antiinflamatorios/uso terapéutico , Homeostasis , Metabolismo Energético
6.
J Transl Med ; 21(1): 516, 2023 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525158

RESUMEN

Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed, uninterrupted loop. The expression of circRNA differs among cell types and tissues, and various circRNAs are aberrantly expressed in a variety of diseases, including cancer. Aberrantly expressed circRNAs contribute to disease progression by acting as microRNA sponges, functional protein sponges, or novel templates for protein translation. Recent studies have shown that circRNAs are enriched in exosomes. Exosomes are spherical bilayer vesicles released by cells into extracellular spaces that mediate intercellular communication by delivering cargoes. These cargoes include metabolites, proteins, lipids, and RNA molecules. Exosome-mediated cell-cell or cell-microenvironment communications influence the progression of carcinogenesis by regulating cell proliferation, angiogenesis, metastasis as well as immune escape. In this review, we summarize the current knowledge about exosomal circRNAs in cancers and discuss their specific functions in tumorigenesis. Additionally, we discuss the potential value of exosomal circRNAs as diagnostic biomarkers and the potential applications of exosomal circRNA-based cancer therapy.


Asunto(s)
Exosomas , Neoplasias , Humanos , ARN Circular/genética , Neoplasias/genética , Carcinogénesis , Transformación Celular Neoplásica , Comunicación Celular , Microambiente Tumoral
7.
Cell Tissue Res ; 393(2): 201-215, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37249708

RESUMEN

Tendon injury is one of the most common disorders of the musculoskeletal system, with a higher likelihood of occurrence in elderly individuals and athletes. In posthealing tendons, two undesirable consequences, tissue fibrosis and a reduction in mechanical properties, usually occur, resulting in an increased probability of rerupture or reinjury; thus, it is necessary to propose an appropriate treatment. Currently, most methods do not sufficiently modulate the tendon healing process and restore the function and structure of the injured tendon to those of a normal tendon, since there is still inadequate information about the effects of multiple cellular and other relevant signaling pathways on tendon healing and how the expression of their components is regulated. microRNAs are vital targets for promoting tendon repair and can modulate the expression of biological components in signaling pathways involved in various physiological and pathological responses. miRNAs are a type of noncoding ribonucleic acid essential for regulating processes such as cell proliferation, differentiation, migration and apoptosis; inflammatory responses; vascularization; fibrosis; and tissue repair. This article focuses on the biogenesis response of miRNAs while presenting their mechanisms in tendon healing with perspectives and suggestions.


Asunto(s)
MicroARNs , Traumatismos de los Tendones , Humanos , Anciano , MicroARNs/genética , Traumatismos de los Tendones/genética , Traumatismos de los Tendones/patología , Tendones/patología , Diferenciación Celular , Fibrosis
8.
Surg Radiol Anat ; 45(10): 1205-1211, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37423946

RESUMEN

PURPOSE: This study intended to compare the difference between the anterior talofibular ligament (ATFL) and posterior talofibular ligament (PTFL) angle with chronic ankle instability (CAI) patients and healthy volunteers, and to confirm whether using the ATFL-PTFL angle could be a reliable assessment method for CAI, so as to improve the accuracy and specificity of clinical diagnosis. METHODS: This retrospective study included 240 participants: 120 CAI patients and 120 healthy volunteers between 2015 and 2021. The ATFL-PTFL angle of the ankle region was gaged in the cross-sectional supine position on MRI between two groups. After participants undergoing a comprehensive MRI scanning, ATFL-PTFL angles were regarded as the main indicator of patients with the injured ATFLs and healthy volunteers to compare, and were measured by an experienced musculoskeletal radiologist. Moreover, other qualitative and quantitative indicators referring to anatomical and morphological characteristics of the AFTL were included in this study with MRI, such as the length, width, thickness, shape, continuity, and signal intensity of the ATFL, which can be used as secondary indicators. RESULTS: In the CAI group, the ATFL-PTFL angle was 90.8° ± 5.7°, which was significantly different from the non-CAI group where the ATFL-PTFL angle for 80.0° ± 3.7° (p < 0.001). As for the ATFL-MRI characteristics, the length (p = 0.003), width (p < 0.001), and thickness (p < 0.001) in the CAI group were also significantly different from the non-CAI group. Over 90% of the cases, patients of the CAI group had injured ATFL with an irregular shape, non-continuous, and high or mixed signal intensity. CONCLUSION: Compared with healthy people, the ATFL-PTFL angle of most CAI patients is larger, which can be used as a secondary index to diagnose CAI. However, the MRI characteristic changes of ATFL may not relate to the increased ATFL-PTFL angle.


Asunto(s)
Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Humanos , Ligamentos Laterales del Tobillo/diagnóstico por imagen , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/anatomía & histología , Estudios Retrospectivos , Tobillo , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Inestabilidad de la Articulación/diagnóstico por imagen
9.
Saudi Pharm J ; 29(4): 305-314, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33994825

RESUMEN

Gossypol (Gos) is a natural polyphenolic compound that has shown a number of valuable biological properties such as antifertility, antioxidation, and antitumor activities. However, the clinical application of Gos has been hindered by its notable adverse effects such as hypokalemia, hemolytic anemia, and so on. Using sustained-release dosage form provides a hopeful solution to this problem. In this study, a gastric floating tablet for sustained-release of Gos (Gos-GFT) was developed using polyvinylpyrrolidone, hydroxypropyl methyl cellulose, ethyl cellulose, lactose, sodium bicarbonate, and magnesium stearate. Gos-GFT had an average weight of around 200 mg with a drug content percentage of around 13.66%. The physicochemical properties of Gos-GFT satisfied the pharmacopoeial requirements for tablets. Gos-GFT was able to float in an acidic medium and had a sustained drug release for over 12 h. In vivo studies showed that the relative bioavailability of Gos-GFT, as compared with Gos powders, was larger than that of a non-gastric floating tablet which was a dosage form used for comparison with Gos-GFT. Furthermore, compared with the Gos powders and the non-gastric floating Gos tablets, Gos-GFT could prolong the in vivo action time of Gos, and significantly relieve hypokalemia which is a major adverse effect of Gos. These properties made Gos-GFT a promising Gos preparation that warrants further investigation for more extensive clinical applications of this natural compound.

10.
Saudi Pharm J ; 27(7): 1000-1008, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31997907

RESUMEN

Dihydromyricetin (DHM) is a natural dihydroflavonol compound with quite a number of important pharmacological properties. However, its low solubility in water and poor stability in aqueous environment, have compromised drug efficacy of DHM, thus hindering its clinical use. The present study was to develop DHM-loaded gastric floating sustained-release tablet (DHM-GFT) to improve the bioavailability of DHM. DHM-GFT was prepared via powder direct compression. The formulation of tablet was optimized in terms of the floating ability and drug release rate. The optimized DHM-GFT exhibited short floating lag time of less than 10 s and long floating duration of over 12 h in acidic medium. It had a 12-hour sustained release of DHM, which proved its potential to develop as a twice-a-day dosing preparation. The physicochemical properties of DHM-GFT well satisfied the pharmacopoeial requirements. In addition, the results from pharmacokinetic studies demonstrated that, DHM-GFT could considerably prolong the in vivo residence time of drug and improve the bioavailability via good gastric floating ability and sustained drug release when compared to DHM powder. Therefore, DHM-GFT is promising to promote the application of DHM and merits studies for further development.

11.
Pain Ther ; 13(5): 1031-1046, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39039345

RESUMEN

INTRODUCTION: Neck pain constitutes a prevalent and burdensome health issue, substantially impairing patients' quality of life and functional capabilities. Kinesio taping (KT), a commonly employed intervention within physical therapy, holds promise for mitigating such symptoms; however, a comprehensive evaluation of its efficacy and evidence base is lacking. Therefore, this study endeavors to systematically investigate the therapeutic effects of KT on both subjective neck pain intensity and objective measures of physical activity limitations through a rigorous meta-analytic approach. By synthesizing existing literature and scrutinizing methodological nuances, we aim to furnish healthcare practitioners with evidence-informed insights, facilitating more judicious clinical decision-making and optimizing patient outcomes. METHODS: According to the PRISMA guidelines, we conducted searches on PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials (RCTs) investigating the efficacy of KT in treating neck pain. Screening was performed based on predefined inclusion and exclusion criteria. Characteristics of the included RCTs were extracted. Trial heterogeneity was assessed using the I2 statistic. Meta-analysis was conducted using Stata 17 software. Risk of bias and methodological quality were evaluated using the Cochrane Risk of Bias 2 tool and the PEDro scale, respectively. RESULTS: In our analysis of 10 RCTs involving 620 patients meeting our inclusion criteria, KT demonstrated significant beneficial effects on neck pain, notably surpassing conventional treatment (weighted mean difference = -0.897, 95% CI -1.30 to -0.49, P < 0.001). Subgroup analysis further revealed that KT exhibited particularly pronounced efficacy in the treatment of nonspecific neck pain and mechanical neck pain, with a more substantial effect observed after 4 weeks of KT intervention compared to 1 week. Moreover, KT demonstrated superior efficacy in alleviating pain symptoms compared to both conventional treatment and sham interventions. CONCLUSION: KT has demonstrated efficacy in reducing neck pain and improving cervical dysfunction among patients. Prolonged KT treatment or its combination with other therapeutic modalities may potentially enhance therapeutic outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024524685.

12.
Sports Health ; : 19417381241277804, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279244

RESUMEN

BACKGROUND: Despite growing applications of backward walking (BW) in assessing and rehabilitating neuromuscular conditions, its effects on gait in chronic ankle instability (CAI) remain unclear. Moreover, linking patient-reported and clinically generated measures is imperative for understanding CAI. HYPOTHESES: Patients with CAI will exhibit worse and compensatory spatio-temporal and kinetic gait parameters during BW, and patient-reported outcomes (PROs) will be correlated significantly with gait parameters. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 46 volunteers participated (23 per group). Patients filled out scales for pain, functions, and fear-avoidance beliefs before testing. All participants walked 6 times each in both forward and backward conditions, and gait was recorded using the Win-Track system. A 2-way mixed analysis of variance was performed to compare gait parameters. The relationship between PRO and gait outcomes was assessed through the Pearson product correlation coefficient. RESULTS: The CAI group demonstrated prolonged support and swing phases, increased walk-off angle, and plantar pressure area, but decreased step length and plantar pressure versus controls (P < 0.05). The CAI group had a smaller right walk-off angle during BW than FW; the control group showed the opposite (P < 0.05). The left single stance duration was greater in the CAI group, while the right was not (P < 0.05). PRO correlated significantly with gait parameters, particularly spatial parameters (P < 0.05). CONCLUSION: The CAI group exhibited worse gait parameters during BW. The CAI group exhibited a characteristic compensatory gait pattern. Linking the self-reported scores provides a better representation of gait changes in CAI. CLINICAL RELEVANCE: These results suggest that BW may be an effective strategy for identifying and evaluating CAI. It may be feasible to apply BW to the rehabilitation of CAI.

13.
Orthop Surg ; 16(5): 1196-1206, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38485459

RESUMEN

OBJECTIVE: The talus is an important component in the ankle, and its treatment after injury is crucial. However, complications and adverse events due to incomplete traditional classifications may still occur, and these classifications fail to analyze the patterns and distribution of fractures from a three-dimensional perspective. Therefore, in this study, we aimed to analyze the location and distribution of fracture lines in different types of talus fractures using three-dimensional (3D) and heat mapping techniques. Additionally, we aimed to determine the surface area of the talus that can be utilized for different approaches of internal fixation, aiding in the planning of surgical procedures. METHODS: We retrospectively analyzed data from CT scans from 126 patients diagnosed with talus fractures at our two hospitals. We extracted the CT data of a healthy adult and created a standard talus model. We performed 3D reconstruction using patients' CT images and superimposed the fracture model onto the standard model for drawing fracture lines. Subsequently, we converted the fracture lines into a heat map for visualization. Additionally, we measured 20 specimens to determine the boundary for various ligaments attached to the talus. We determined the surface area of the talus available for different surgical approaches by integrating the boundary data with previously reported data on area of exposure. RESULTS: Without considering the displacement distance of the fracture, fracture types were classified as follows, by combining Hawkins and Sneppen classifications: talar neck, 41.3%; posterior talar tubercle, 22.2%; body for the talus and comminuted, 17.5%; lateral talar tubercle, 11.9%; and talar head, 7.1%. We established fracture line and heat maps using this classification. Additionally, we demonstrated the available area for anteromedial, anterolateral, posteromedial, posterolateral, and medial malleolus osteotomy and Chaput osteotomy approaches. CONCLUSION: Fracture line and heat map analyses can aid surgeons in planning a single or combined surgical approach for the reduction and internal fixation of talus fractures. Demonstrating the different surgical approaches can help surgeons choose the most effective technique for individual cases.


Asunto(s)
Fijación Interna de Fracturas , Fracturas Óseas , Imagenología Tridimensional , Astrágalo , Tomografía Computarizada por Rayos X , Humanos , Astrágalo/lesiones , Astrágalo/cirugía , Astrágalo/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/clasificación , Anciano , Adulto Joven , Adolescente , Fracturas de Tobillo/cirugía , Fracturas de Tobillo/diagnóstico por imagen
14.
Artículo en Inglés | MEDLINE | ID: mdl-39331480

RESUMEN

OBJECTIVE: The study was designed to explore the effect of proprioceptive training in contrast to conventional training among individuals following anterior cruciate ligament reconstruction (ACLR). It includes joint position sense (JPS), subjective functional outcomes (Cincinnati, Knee injury Osteoarthritis Outcome Score, International Knee Documentation Committee knee form), muscle strength, pain, and kinesthesia. METHODS: PubMed, EMBASE, The Cochrane Library, and Web of Science databases were searched. Quality assessment was performed through the Cochrane Risk of Bias tool and GRADE system. The standardized mean deviation (SMD) was selected as the effect size. RESULTS: Fifteen studies and 537 participants were included. Compared with conventional training, proprioceptive training may significantly enhance passive JPS (SMD = -1.87 [95%CI: -2.39 to -1.34]) and single-leg hop function test performance (SMD = 0.29 [95%CI 0.04 to 0.54]). Data also indicated that proprioceptive training can moderately improve subjective functional outcomes (SMD = 0.61 [95%CI, 0.23 to 0.99]). However, there were no significant effects on active JPS, muscle strength and VAS. CONCLUSION: Proprioceptive training has the potential to yield beneficial effects on knee passive JPS, hop functional test and subjective functional outcomes in patients after ACLR. However, its impact on enhancing knee active JPS and kinesthesia may not be statistically significant.

15.
Int Immunopharmacol ; 143(Pt 1): 113359, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39388895

RESUMEN

Inflammation and extracellular matrix (ECM) degradation are two major factors involved in the pathogenesis of osteoarthritis (OA). Wedelolactone, a natural compound classified as a coumestan, is isolated from the medicinal plants Eclipta alba and Wedelia calendulacea. In this study, we assessed the protective effects of Wedelolactone on chondrocytes in OA. Our findings show that pretreatment with Wedelolactone effectively inhibited the IL-1ß-induced upregulation of COX­2, iNOS, TNF-α, and IL6 in chondrocytes, contributing to inflammation suppression. Moreover, pretreatment with Wedelolactone followed by IL-1ß treatment significantly increased the expression of Collagen II and SOX9, while decreasing the expression of Adamts5, MMP1, MMP3, and MMP13, thereby promoting ECM protection. Through Network pharmacology Analysis, we identified 14 key targets that link Wedelolactone and OA. GO and KEGG pathway analysis suggested that Wedelolactone primarily impacted OA by targeting inflammatory responses, particularly the NF-κB signaling pathway. Further studies demonstrated Wedelolactone prevented IL-1ß-induced activation of NF-κB signaling pathway by inhibiting the translocation of p65 and the preventing the degradation of IκBα in human chondrocytes. Molecular docking studies also indicated that Wedelolactone can directly bind to the NF-κB complex, thereby inhibited the nuclear localization of p65. In vivo experiments demonstrated that Wedelolactone can alleviate cartilage damage in DMM mice model. In summary, Wedelolactone appears to mitigate inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway, thereby alleviating OA progression. Our results suggested Wedelolactone may offer therapeutic advantages for OA treatment.

16.
Orthop Surg ; 16(8): 1770-1782, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38946017

RESUMEN

Fractures and bone nonunion commonly require surgical intervention. Serious outcomes of non-healing in the late stages of fracture place a significant financial burden on society and families. Bone nonunion occurs when a fracture stops healing, for many reasons, and leads to a variety of bad outcomes. Numerous factors, including biomechanics and immunology, are involved in the complicated mechanisms of bone nonunion. The immune-inflammatory response plays a significant part in the emergence of bone nonunion, and the occurrence, control, and remission of inflammation in the bone healing process have a significant influence on the ultimate success of bone tissue repair. In the bone microenvironment, immune cells and associated cytokines control bone repair, which is significantly influenced by macrophages, T cells, and fibroblast growth factor. To limit acute inflammation and  balance osteogenesis and osteoblastogenesis for tissue repair and regeneration, immune cells and various cytokines in the local microenvironment must be precisely regulated. As a bad complication of late-stage fractures, bone nonunion has a significant effect on patients' quality of life and socioeconomic development. Therefore, in-depth research on its pathogenesis and treatment methods has important clinical value. To provide more precise, focused therapeutic options for the treatment of bone nonunion, we discuss the regulatory roles of the key immune cells engaged in bone healing within the microenvironment during bone healing and their effect on osteogenesis.


Asunto(s)
Curación de Fractura , Fracturas no Consolidadas , Humanos , Curación de Fractura/fisiología , Inmunomodulación
17.
Cell Biochem Biophys ; 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39306824

RESUMEN

Osteoarthritis (OA) is a prevalent joint disease affecting orthopedic patients. Its incidence is steadily increasing, causing great economic hardship for individuals and society as a whole. OA is connected with risk factors such as genetics, obesity, and joint diseases; yet, its pathophysiology is still largely understood. At present, several cell death pathways govern the initiation and advancement of OA. It has been discovered that the onset and progression of OA are strongly associated with pyroptosis, senescence, apoptosis, ferroptosis, and autophagy. Ferroptosis and autophagy have not been well studied in OA, and elucidating their molecular mechanisms in chondrocytes is important for the diagnosis of OA. For this reason, we aim was reviewed recent national and international developments and provided an initial understanding of the molecular pathways underlying autophagy and ferroptosis in OA. We determined the reference period to be the last five years by searching for the keywords "osteoarthritis, mechanical stress, Pizeo1, ferroptosis, autophagy, ferritin autophagy" in the three databases of PUBMED, Web of Science, Google Scholar. We then screened irrelevant literature by reading the abstracts. Ferroptosis is a type of programmed cell death that is dependent on reactive oxygen species and Fe2+. It is primarily caused by processes linked to amino acid metabolism, lipid peroxidation, and iron metabolism. Furthermore, Piezoelectric mechanically sensitive ion channel assembly 1 (PIEZO1), which is triggered by mechanical stress, has been revealed to be intimately associated with ferroptosis events. It was found that mechanical injury triggers changes in the intracellular environment of articular chondrocytes (e.g., elevated levels of oxidative stress and increased inflammation) through PIEZO1, ultimately leading to iron death in chondrocytes. Therefore, we believe that PIEZO1 is a key initiator protein of iron death in chondrocytes. Widely present in eukaryotic cells, autophagy is a lysosome-dependent, evolutionarily conserved catabolic process that carries misfolded proteins, damaged organelles, and other macromolecules to lysosomes for breakdown and recycling. Throughout OA, autophagy is activated to differing degrees, indicating that autophagy may play a role in the development of OA. According to recent research, autophagy is a major factor in the process that leads cells to ferroptosis. Despite the notion of ferritinophagy being put forth, not much research has been done to clarify the connection between ferroptosis and autophagy in OA.

18.
Front Bioeng Biotechnol ; 12: 1326036, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38515619

RESUMEN

Background: The transfer of the anterior tibiofibular ligament distal fascicle (ATiFL-DF) for the augmentation repair of the anterior talofibular ligament (ATFL) shows potential as a surgical technique. However, evidences on the benefits and disadvantages of this method in relation to ankle joint function are lacking. Purpose: This study aimed to provide comprehensive experimental data to validate the feasibility of ATiFL-DF transfer augmentation repair of the ATFL. Methods: This study included 50 embalmed ankle specimens to measure various morphological features, such as length, width, thickness, and angle, for evaluating similarities between the ATiFL-DF and ATFL. Furthermore, 24 fresh-frozen ankle specimens were examined for biomechanical testing of the ATiFL-DF transfer augmented repair of the ATFL. Finally, 12 pairs of ATiFL-DF and ATFL tissues from fresh-frozen ankle specimens were treated with gold chloride staining to analyze mechanoreceptor densities. Results: Anatomical studies found that the lengths and thicknesses of the ATFL and ATiFL-DF are similar. Biomechanical outcomes showed that performing ATiFL-DF transfer for ATFL repair can improve the stability of the talus and ankle joints. This is evident from the results of the anterior drawer, axial load, and ultimate failure load tests. However, performing ATiFL-DF transfer may compromise the stability of the distal tibiofibular joint, based on the Cotton and axial load tests at an external rotation of 5°. Analysis of the histological findings revealed that mechanoreceptor densities for four types of mechanoreceptors were comparable between the ATiFL-DF and ATFL groups. Conclusion: ATiFL-DF transfer is a viable method for augmenting ATFL repair. This technique helps to improve the stability of the talus and ankle joints while compensating for proprioception loss. Although ATiFL-DF transfer augmented repair of the ATFL may negatively affect the stability of the distal tibiofibular joint, this procedure can enhance the stability of the talus and ankle joints.

19.
Pharmaceutics ; 16(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38931926

RESUMEN

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.

20.
Orthop Surg ; 15(10): 2557-2565, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37537373

RESUMEN

OBJECTIVES: The role of the distal tibiofibular ligament in the occurrence of high ankle sprain (HAS) has been widely studied. But previous studies have overlooked the physiological and anatomical differences between males and females and have not further refined gender. Therefore, the impact of the anatomical morphology of fibular notch (FN) on HAS in different genders is still unclear. This study aimed to explore the impact of different types of FN on the severity of HAS and to estimate the prognosis of patients with HAS while excluding anatomical differences caused by gender. METHODS: One hundred and eighty patients with HAS were included in this study as the experimental group (i.e., HAS group). They were further divided into four groups according to gender and FN depth, with deep concave FN ≥ 4 mm and shallow flat FN < 4 mm. Another 180 normal individuals were set as the control group. The FN morphological indicators, tibiofibular distance (TFD), and ankle mortise indexes were measured and compared with those in HAS group. The independent t-test was used to compare continuous variables between groups, the intraclass correlation coefficient (ICC) was used to analyze the reliability of intra-observer measurement, and the Pearson correlation coefficient was used to verify the correlation between FN and the severity of HAS. RESULTS: In males with shallow flat type, the measurements of anterior tibiofibular distance (aTFD), middle tibiofibular distance (mTFD), posterior tibiofibular distance (pTFD), front ankle mortise width (fAMW), middle ankle mortise width (mAMW), posterior ankle mortise width (pAMW), and depth of ankle mortise (DOAM) in HAS group were significantly larger than those in normal group (p < 0.05). In male patients with deep concave type, the measurements of aTFD, mTFD, fAMW, mAMW, and DOAM were significantly larger than those in normal group (p < 0.05). Among female patients with shallow flat type, the measurements of aTFD, mTFD, pTFD, fAMW, mAMW, pAMW, and DOAM were found to be significantly larger than those in normal group (p < 0.05). Among female patients with deep concave type, the measurements of mTFD, pTFD, fAMW, mAMW, and DOAM were found to be significantly larger than those of the normal group (p < 0.05). The depth of FN was negatively correlated with TFD, and the AOFAS score of patients with shallow flat type was significantly lower than that of patients with deep concave type after treatment (p < 0.05). CONCLUSIONS: In different gender groups, compared with the normal controls, the TFD and partial ankle mortise indices were significantly different in HAS patients. Moreover, FN depth was negatively correlated with TFD, and the AOFAS score of shallow flat patients was significantly lower than that of deep concave patients. These suggested that shallow flat FN may be associated with more severe distal tibiofibular ligament injury and ankle mortise widening, leading to poorer prognosis. This should be taken seriously in clinical practice.


Asunto(s)
Traumatismos del Tobillo , Articulación del Tobillo , Humanos , Masculino , Femenino , Estudios Retrospectivos , Reproducibilidad de los Resultados , Pronóstico , Peroné
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